Loss of positional signals may slow skin repair by disrupting tissue organization
Repeated skin injury may corrupt signals that tell repairing cells where they belong, slowing functional recovery despite continued collagen production. The mechanism is rejected if correctly arranged signals offer no repair advantage or its prediction cannot be separated from total tissue loss.
Stage of verification
- Hypothesis published2026-09-25
- Indirect evidenceAssessed at 4 of 10
- Direct testAwaited
Map of the hypothesis
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Target map
Every target of every published hypothesis, each with the actions a hypothesis can propose on it. The targets and the actions of this hypothesis are drawn solid.

Signalling pathway
Positional signaling
Combinations of signals that guide cells in establishing their position and function within tissue
Where this hypothesis actsSurviving cells around skin microinjuries during repeated fractional procedures
Hypotheses on this target 2
Inhibition
Activation
Desensitisation
Function preservation
Feedback restoration
Rhythm restoration
What is proposed
Restore the spatial arrangement and preserve the redundancy of positional signals
With whatTargeted delivery
HowLocally control signal expression or delivery in organized skin cultures to restore the correct spatial combinations
Possible result
Possible faster functional repair and stabilization of SPV_9
From the recordВ модели повторного повреждения пространственно правильное восстановление этих сигналов должно ускорять ремонт
All targets of the lab
Every target read from the published hypotheses, each kind around its pictogram. A larger mark means more hypotheses act on that target. Point at a mark and the actions proposed on it branch out of it.
Solid and named: the targets of this hypothesis
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The logic
The train of thought that ends in this hypothesis. Each stage is the reason the next exists. The master question narrows to a goal, the goal to an unknown nobody has closed, the unknown to the hypothesis proposed here. Every step below says what it rests on and what carries it.
Skin that produces more structural material after treatment may still become slower at recovering its protective barrier, strength and sensitivity. The unexpected move is to propose that repeated injury damages the surrounding cells' instructions about where repaired structures belong, while leaving cells able to make material. This is a hypothesis generated by the pipeline, not a measured explanation of declining skin repair.
- Surviving cells around an injury provide overlapping cues about the correct locations and roles of repairing cells.
- Repeated procedures remove or alter components of those cue combinations.
- The proposed cue-reading system changes from correcting missing or incorrect information to leaving some location errors unresolved.
- Repairing cells remain alive and produce collagen but build incorrect relationships between skin layers and nerve endings.
- Incorrect tissue organization slows subsequent recovery of protection, strength and sensitivity.
- Preserving enough correctly arranged cues is predicted to keep functional recovery stable across repeated injuries.
A street can remain navigable after some signs disappear if house numbers and other signs still identify each destination. Moving the remaining signs to the wrong corners can misdirect deliveries even when the total number of signs stays the same.
Where the picture breaks: Skin cells have not been shown here to read a fixed set of location labels. Unlike street signs, the relevant biological cues, their combinations and the rules for resolving conflicting information still have to be established.
- Master questionstep 01 of 04
A therapy is sought that would bring the functional condition of middle-aged people's skin closer to that of young people's skin.
Rests on: The stated goal is improvement in how skin functions, with young people's skin as the reference.
Stated in the chain - Goal pillarstep 02 of 04
The desired therapy would restore skin functions completely and keep them restored.
Rests on: The goal of reaching youthful function is extended to require complete and lasting restoration.
AssumptionCompleteness and durability are adopted as requirements; the master question does not explicitly specify either.
- Gap questionstep 03 of 04
Repeated fractional treatment, which injures small separated areas of skin, might deplete the skin's remaining capacity to repair itself even while collagen, a structural protein, increases. The proposed warning sign is progressively slower recovery of the protective barrier, strength and sensitivity after the same everyday challenge.
Rests on: Lasting functional restoration requires attention to recovery across repeated treatments, rather than material accumulation alone.
Stated in the chain - Hypothesisstep 04 of 04
Surviving cells around small injury sites are proposed to carry overlapping positional signals, meaning cues that tell repairing cells where they belong and what role to take. Repeated procedures could corrupt enough cues that cells remain alive and make collagen but assemble the skin's outer layer, deeper supporting layer and nerve endings incorrectly, slowing later repair.
Rests on: The preceding question supplies the possible separation between collagen production and functional recovery. The proposed explanation borrows from error-correcting codes, arrangements of information that allow missing or incorrect parts to be recovered.
AssumptionThe biological assumption is that skin uses overlapping combinations of location cues through a system that can correct some missing or incorrect cues, and that repeated injury can overwhelm this ability. The preceding question does not establish that system; the mathematical borrowing supplies a proposed model, not biological evidence.
What is carried, and what is not. None of the supplied screened sources directly establishes the proposed causal links from repeated injury through cue loss to slower functional repair. S5, a 2019 review in Physiological Reviews, describes wound healing as requiring coordination of different cell types across space and time, but does not establish this cue-correction mechanism or the sequence end to end.S5
Where the reasoning is carried by something unstated · 2
- Goal pillar. Completeness and durability are adopted as requirements; the master question does not explicitly specify either.
- Hypothesis. The biological assumption is that skin uses overlapping combinations of location cues through a system that can correct some missing or incorrect cues, and that repeated injury can overwhelm this ability. The preceding question does not establish that system; the mathematical borrowing supplies a proposed model, not biological evidence.
How a result here could mislead · 3
- A benefit from correctly arranged signals could be credited to restored location information even if that arrangement instead changes cell survival, tissue loss or the amount of collagen. What closes it: The comparison must verify the specified matching of injury area and depth, surviving cell numbers and collagen, alongside equal total amounts of the supplied signals. Tissue organization and functional recovery must also be measured.
- A boundary between recoverable and unrecoverable cue patterns could appear predictive because the signals and their categories were chosen after seeing which samples healed. What closes it: The causally relevant signals, rules for classifying their states and predicted boundary must be fixed before evaluation on new samples. Prediction must remain informative beyond total tissue loss; crossing the mathematical guarantee's boundary alone does not establish biological failure.
- Improved repair could be attributed specifically to location cues while leaving the rival explanations unresolved: repeated copying of cells' genetic material without cell division, or repeated damage to incompletely repaired sensory nerves. A culture without functioning nerves also cannot establish restored sensitivity. What closes it: Distinguishing these routes requires measurements of genetic-material copies and cell size, together with nerve recovery, across the correctly arranged and shuffled-signal conditions. The supplied plan reserves full sensitivity testing for a model containing nerves, but does not specify these rival-mechanism controls.
What would make this wrong. The specified mechanism would be contradicted if verified restoration of causally established location cues in the correct arrangement offered no repair advantage over the same cues in a shuffled arrangement under the stipulated matched conditions. Its predictive claim would also fail if the previously measured correction boundary did not predict deterioration in new samples independently of total tissue loss. These conclusions require successful delivery of the intended cue patterns; unsuccessful manipulation would leave the mechanism unresolved.
What it would change. If the mechanism held, restoring youthful skin function would require preserving the information that organizes repair, alongside maintaining living cells and structural material. Repeated-treatment evaluation would have to follow tissue arrangement and recovery of protection, strength and sensitivity. Success in organized skin cultures would still not establish complete, durable restoration in middle-aged people, and sensitivity would remain unestablished without the separate model containing nerves.
Sources read · 10
Transcriptomic analysis of human skin wound healing and rejuvenation following ablative fractional laser treatment. · PloS one · 2021
“Skin wound healing involves inflammatory, epidermal and dermal processes”
Does not settle: Источник описывает транскрипционные изменения после фракционного лазерного воздействия, но не устанавливает утрату позиционных сигналов, пространственные отношения между эпидермисом, дермой и нервными окончаниями, замедление функционального ремонта после повторных процедур или SPV_9.
Rapid healing of scar-associated chronic wounds after ablative fractional resurfacing. · Archives of dermatology · 2012
“All patients experienced incidental rapid healing of their chronic wounds within 2 weeks of their initial ablative fractional laser treatment.”
Does not settle: This abstract reports three patients after an initial treatment. It does not establish effects of repeated procedures, positional signals, epidermis-dermis-nerve spatial relationships, collagen synthesis, or SPV_9.
Hypertrophic scarring of the neck following ablative fractional carbon dioxide laser resurfacing. · Lasers in surgery and medicine · 2009
“Fractional photothermolysis is a method of skin rejuvenation that produces a unique thermal damage pattern characterized by multiple columns of thermal damage, known as microthermal treatment zones (MTZs) surrounded by untreated tissue.”
Does not settle: Источник не устанавливает роль позиционных сигналов, их избыточности или стирания при повторных процедурах; не оценивает пространственные отношения между эпидермисом, дермой и нервными окончаниями, последующий функциональный ремонт или SPV_9.
Monitoring of wound healing process of human skin after fractional laser treatments with optical coherence tomography. · Biomedical optics express · 2013
“The results showed that the coagulation damage induced by the NAFLs could be rapidly healed in 6 days. In contrast, the tissue volatilization induced by AFLs required a longer recovery time of 14 days.”
Does not settle: Источник не исследует позиционные сигналы, пространственные отношения между эпидермисом, дермой и нервными окончаниями, повторные процедуры или их влияние на последующий функциональный ремонт.
Wound Healing: A Cellular Perspective. · Physiological reviews · 2019
“Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis, inflammation, growth, re-epithelialization, and remodeling.”
Does not settle: Источник оставляет открытыми роль позиционных сигналов, последствия повторных процедур, порог коррекции ошибок, пространственные отношения между эпидермисом, дермой и нервными окончаниями, а также связь этих факторов с последующим функциональным ремонтом и SPV_9.
Spatiotemporal single-cell roadmap of human skin wound healing. · Cell stem cell · 2025
“Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored.”
Does not settle: Источник не устанавливает существование избыточных сочетаний позиционных сигналов вокруг микрозон повреждения, их утрату при повторных процедурах, нарушение отношений между эпидермисом, дермой и нервными окончаниями или замедление последующего функционального ремонта.
Single cell transcriptomic landscape of diabetic foot ulcers. · Nature communications · 2022
“The distinct and previously undescribed subtype or state of fibroblasts, HE-Fibro, with overexpression of matrix remodeling, immune and inflammatory genes, may contribute to successful wound repair in DFU-Healers.”
Does not settle: Источник не устанавливает роль позиционных сигналов, последствия повторных процедур или нарушение пространственных отношений между эпидермисом, дермой и нервными окончаниями. Он также не оценивает SPV_9 и не демонстрирует, что сохранение избыточности таких сигналов ускоряет функциональный ремонт.
Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing. · Stem cell research & therapy · 2023
“Wound healing is a highly sequential process of skin barrier function restoration and consists of temporally overlapping and interdependent phases, including hemostasis, inflammation, proliferation, and tissue remodeling”
Does not settle: Источник не устанавливает роль позиционных сигналов, последствия повторных процедур, нарушение пространственных отношений между эпидермисом, дермой и нервными окончаниями или влияние таких нарушений на скорость последующего функционального ремонта.
Curcumin-Loaded Nanocomposite Hydrogel Dressings for Promoting Infected Wound Healing and Tissue Regeneration. · International journal of nanomedicine · 2024
“These images exhibited an increase in collagen accumulation in all groups, with relatively sparse collagen accumulation in the control group and tightly aligned and organised collagen accumulation in the Gel@Cur and GelMA/AHA-Gel@Cur groups.”
Does not settle: It does not test positional-signal redundancy, repeated procedures, error-correction limits, epidermis–dermis–nerve spatial relationships, SPV_9, or whether disruption of such signals slows later functional repair.
Mapping epidermal and dermal cellular senescence in human skin aging. · Aging cell · 2025
“These findings portend a novel architectural blueprint of the epidermis and dermis based on hallmarks of aging for human skin.”
Does not settle: Источник не изучает микрозоны повреждения, повторные процедуры, скорость или функциональные исходы заживления, синтез коллагена, нервные окончания, причинную роль позиционных сигналов или SPV_9.
The gap this hypothesis explains
Two live hypotheses pull in opposite directions here, and the field has not chosen between them.
Does repeated treatment of tiny skin areas deplete repair capacity even when collagen increases?
Original wording · exactly as the pipeline generated it
Ускоряет ли повторное фракционное воздействие истощение регенеративного резерва, несмотря на рост коллагена, если после одинаковой бытовой нагрузки восстановление барьера, прочности и чувствительности замедляется от цикла к циклу?
What this question is asking
The question concerns whether repeated skin treatment preserves the ability to recover from everyday stress or gradually wears that ability down. It asks whether fractional treatment, which acts on small areas within the treated skin, accelerates loss of repair capacity if later treatment cycles are followed by slower recovery of the skin’s protective barrier, strength and sensitivity after the same everyday stress. It assumes that collagen can increase alongside this functional decline, but that combination is not established by the supplied evidence. The relevant comparison is recovery after successive cycles versus earlier cycles and skin receiving fewer or no treatments; the stated longer-term requirement is recovery as fast as in young skin, with acceptable safety, for at least 10 years.
- Fractional treatment
- Treatment delivered to small areas within a larger skin region. The supplied sources discuss laser approaches and also a comparison involving radiofrequency; the input does not identify one precise treatment method or schedule for the proposed question.
- Fractional laser treatment and microscopic treatment zones
- Laser treatment uses light to act on tissue. S3 calls the small wounds created by its fractional approach microscopic treatment zones; these are the local injuries from which healing follows.
- Radiofrequency treatment
- A treatment category using energy from radiofrequency electrical signals. It appears as a comparator in S4, but the supplied quotation does not establish its effects on repeated functional recovery.
- Treatment cycle
- One treatment episode and its subsequent recovery period in the question’s repeated sequence. Multiple passes during one procedure do not by themselves establish multiple cycles separated by recovery.
- Regenerative reserve or repair capacity
- The proposed remaining ability of skin to repair damage over repeated challenges. The input does not define a directly measured quantity or a threshold at which this reserve counts as depleted.
- Collagen
- A structural protein that helps give skin support and strength and also forms part of scar tissue. Its amount and its organization are different properties; the supplied findings do not establish that either alone measures recovery capacity.
- Skin barrier
- The skin’s protective function at its surface. Barrier recovery means restoration of that protection after disruption, rather than simply a change in appearance.
- Skin strength
- The skin’s ability to withstand physical forces without damage. The input does not specify how this would be measured after everyday stress.
- Skin sensitivity
- The skin’s ability to register sensation. The input does not specify which sensations or measurements would count as recovery.
- Fibroblast activation
- Increased activity in cells that produce collagen and other supporting material in skin. S9 reports signs of this activity, which is distinct from demonstrating increased long-term repair capacity.
- Fibrosis
- Accumulation of scar-like supporting tissue. The pipeline raises it as a possible consequence of repeated stimulation, but the supplied evidence does not establish that consequence in the proposed setting.
- Carbon dioxide laser
- A laser named for the gas used to generate its treatment light. Sources describing this laser concern particular treatment settings and do not establish the effects of every fractional method.
- Low-intensity green laser treatment
- An additional light treatment used after fractional laser exposure in S10. Its reported effect cannot be treated as the effect of fractional treatment alone.
- Skin graft
- Skin moved to cover another area of the body. S2 includes treatment of these areas as well as burn scars, which differs from treatment aimed at restoring youthful function in middle-aged skin.
- Depressed acne scars
- Indented scars left after acne. S8 concerns these scars, rather than recovery of otherwise unspecified middle-aged skin after everyday stress.
- Hypertrophic and keloid scars
- Two forms of raised scarring: hypertrophic scars remain within the original injury area, while keloid scars extend beyond it. S5 addresses treatment effectiveness for these conditions.
Collagen can increase after fractional treatment while recovery of the skin barrier, strength and sensitivity after identical everyday stress slows from cycle to cycle, potentially indicating depletion of regenerative reserve.
Collagen is a structural protein in skin, while regenerative reserve means the proposed capacity to keep repairing damage over repeated challenges. The question entertains a mismatch in which more structural material accompanies progressively poorer recovery of protection, strength and sensation. That mismatch would make increased collagen an insufficient sign that repeated treatment preserves youthful function.
S8 describes stimulation of collagen fibers, and S9 reports collagen reorganization and signs of activation in collagen-producing cells. These support a narrower premise that fractional treatment can affect collagen, not the full claim that collagen increases while functional recovery deteriorates across cycles. None of the supplied sources establishes that deterioration or identifies depletion of repair capacity as its cause. The supplied input labels earlier pipeline nodes as allowing depletion and fibrosis, but provides no source evidence establishing those claims.S8S9
The same question asked without the part nothing read establishes:
- Does repeated fractional skin treatment change recovery of protection, strength and sensitivity after identical everyday stress, and how do those changes relate to collagen?
- Does repeated fractional skin treatment preserve recovery as fast as in young skin and acceptable safety for at least 10 years?
- Repeated treatment depletes repair capacity Under this conditional outcome, successive treatments reduce the skin’s remaining ability to repair itself, so the same later stress is followed by slower recovery. If collagen also increases, that increase would coexist with declining function and would not establish lasting restoration to a youthful condition.
- Repeated treatment preserves repair capacity Under this conditional outcome, successive treatments leave the ability to recover intact despite repeated exposure. Collagen changes could then coexist with preserved function, although the separate requirement for acceptable safety over at least 10 years would still need to be established.
- Recovery slows, but depletion is not established Under this conditional outcome, slower recovery demonstrates a functional change without identifying why it occurs. Calling that change depletion of repair capacity would go beyond the evidence, even if increased collagen were documented at the same time.
The proposed concern follows a sequence: treatment affects small areas of skin, healing follows, and the skin must still recover from later everyday stress. A source describes fractional laser treatment as creating small wounds, while other sources describe collagen production or reorganization after treatment; these findings concern different parts of that sequence [S3, S8, S9]. If collagen increases while recovery becomes slower, counting collagen alone would miss the functional deterioration described in the question. Conversely, treating slower recovery as proof that repair capacity has been exhausted would assign a cause that the supplied sources have not established.
Фракционное воздействие RL-3 улучшает отдельные показатели; узлы RL-1 и RL-2 допускают истощение резерва и фиброз при повторной стимуляции.
Повторное лечение сохраняет молодую скорость функционального восстановления и приемлемую безопасность на протяжении минимум 10 лет.
Рост коллагена может сопровождаться ухудшением восстановления после последующих нагрузок; направленность накопленного эффекта требует прямой проверки.
The mechanism it proposes
The engine's own statement of the hypothesis, in full.
Неповрежденные клетки вокруг микрозон повреждения содержат избыточные сочетания позиционных сигналов, по которым восстанавливающиеся клетки определяют свое место и функцию. Повторные процедуры стирают или искажают разные компоненты этих сочетаний. После превышения способности системы исправлять ошибки клетки сохраняют жизнеспособность и способность синтезировать коллаген, но все чаще формируют неверные пространственные отношения между эпидермисом, дермой и нервными окончаниями. Это непосредственно замедляет последующий функциональный ремонт. Сохранение достаточной избыточности позиционных сигналов должно стабилизировать SPV_9.
Where the idea comes from
The hypothesis borrows a result from another field. This is what it borrows, and from where.
Теория кодирования, граница однозначного исправления ошибок и стираний: 2e + s < d_min. Кодовое слово c представляет заранее определенное сочетание состояний n причинно проверенных позиционных сигналов вокруг восстанавливающейся микрозоны; n является числом этих сигналов. Каждый сигнал дискретизируется по установленным до анализа правилам. Множество C содержит допустимые сочетания для разных функциональных положений клеток. d_min является минимальным расстоянием Хэмминга между различными словами C, то есть минимальным числом различающихся сигналов. e обозначает число сигналов с неправильным состоянием, s обозначает число отсутствующих сигналов, отсутствие которых распознается клеткой. Предполагаемый биологический декодер представляет сеть рецепторов и регуляторов дифференцировки. Неравенство дает гарантию исправимости для идеализированной кодовой модели; нарушение неравенства снимает гарантию, но само по себе не означает обязательный биологический отказ. Наличие такого декодирования в коже является проверяемой гипотезой. Основа переноса: [Shannon, A Mathematical Theory of Communication](https://bayes.wustl.edu/Manual/shannon1948.pdf).
Testing and possible results
The prediction that would tell it apart
A hypothesis that predicts what its rivals predict is not worth running an experiment over. This is the observation on which this one differs.
При одинаковых площади и глубине повреждения, числе выживших клеток и количестве коллагена восстановление должно зависеть от сохранности конкретных сочетаний позиционных сигналов. В модели повторного повреждения пространственно правильное восстановление этих сигналов должно ускорять ремонт; те же молекулы в тех же суммарных количествах, но с перемешанным расположением, такого эффекта не дадут. Предварительно измеренная граница исправимости ошибок должна предсказывать ухудшение на новых образцах. Отсутствие преимущества правильного расположения или независимости предсказания от общей потери ткани опровергнет механизм.
States a measurable outcome; comparing rivals needs more conditions. The prediction specifies a qualitative repair comparison under matched molecular quantities, a predictive outcome in new samples, and explicit rejection conditions. No rival prediction is supplied. Only a bench experiment would settle it.
What testing it would take
The engine's own read on whether this is testable with methods that already exist.
Позиционные программы можно измерять пространственными методами, а причинную роль проверять в организованных культурах кожи с локально управляемой экспрессией или подачей сигналов. Сначала необходимо установить, какие сигналы действительно задают положение клеток. Одной корреляции транскриптома с анатомической областью недостаточно. Полную проверку чувствительности проводят отдельно в иннервированной модели.
Other explanations
Every other hypothesis the engine wrote for the same gap, and the observation that would separate the two.
При одинаковых площади и глубине повреждения, числе выживших клеток и количестве коллагена восстановление должно зависеть от сохранности конкретных сочетаний позиционных сигналов. В модели повторного повреждения пространственно правильное восстановление этих сигналов должно ускорять ремонт; те же молекулы в тех же суммарных количествах, но с перемешанным расположением, такого эффекта не дадут. Предварительно измеренная граница исправимости ошибок должна предсказывать ухудшение на новых образцах. Отсутствие преимущества правильного расположения или независимости предсказания от общей потери ткани опровергнет механизм.
- Rival 01 of 02What would separate them
Repeated fractional skin injury may slow repair by doubling genomes without cell division predicts: В отслеживаемых клеточных линиях увеличение плоидности должно предшествовать замедлению восстановления после следующей нагрузки. В доклинической модели предотвращение повторного удвоения генома без цитокинеза должно сохранять скорость восстановления барьера, механических свойств и иннервации при сопоставимых исходном повреждении, жизнеспособности и числе клеток. Пространственно правильная подача регенеративных сигналов или восстановление нервной активности без изменения плоидности не должны полностью устранять дефект. Отсутствие накопленной полиплоидизации либо сохранение функционального ухудшения после ее предотвращения опровергнет гипотезу.
- Rival 02 of 02What would separate them
Repeated fractional treatment may slow skin recovery by injuring regrowing sensory axons predicts: Ухудшению барьерного и механического восстановления должно предшествовать увеличение времени реиннервации и снижение вызванного нейропептидного ответа. Селективное сохранение аксонов при сопоставимом повреждении других тканей должно предотвращать ухудшение всех трех направлений. В доклиническом опыте восстановление сигнала пептида CGRP при сохраняющейся денервации должно улучшать часть барьерного и репаративного ответа, но оставлять сенсорный дефицит; восстановление самих аксонов должно устранять и его. Нормальная иннервация и отсутствие эффекта ее селективного сохранения опровергнут эту гипотезу.
What stands behind it
Which of the figures above have a study behind them, which are the engine's own, and what it would take to refute the hypothesis. This audit never judges the idea.
This hypothesis states no figure and cites no study, so there is nothing here to trace.
What it would take to refute it. Nothing already retrieved carries the prediction’s terms and it names no measurement this layer can route to a public dataset, so the bench is the residual — not a finding against it.
6 papers retrieved around this hypothesis
- Fundamental limits incorporating logical reasoning into Shannon's information theory.PMID 42658762 · full_text · 76,542 characters stored
- The power of theory in the life sciences.PMID 42758128 · full_text · 30,321 characters stored
- The Measurement Problem in the Thermodynamics of Black Holes.PMID 42511417 · full_text · 97,550 characters stored
- Semantic Channel Capacity of Rayleigh Fading Channels Based on Synonymous Mappingeuropepmc:PMC:PMC13297844 · full_text · 52,095 characters stored
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0 citation handles extracted; 1 Europe PMC search run; 0 records examined; 0 sources stored for enrichment, 0 with full text. A citation that did not resolve is a bibliographic failure, not proof that no such paper exists, and no hypothesis is blocked by this audit.