Miracle-dz/UniFAR-FTUs huggingface dataset:
Divisive Normalization Predicts Adaptation-Induced Response Changes in Macaque Inferior Temporal Cortex

Stimulus repetition alters neural responses to the repeated stimulus. This so-called adaptation phenomenon has been commonly observed at multiple spatial and temporal scales and in different brain areas, and has been hypothesized to affect the neural representation of the sensory input. Yet, the neural mechanisms underlying adaptation still remain unclear, especially in higher-order cortical areas. Here we employ a divisive normalization model of neural responses to predict adaptation-induced changes in responses of single neurons in the macaque inferior temporal (IT) cortex. According to this model, the response of a neuron is determined by an interplay between its direct excitatory and divisive normalizing inputs, with each input being subject to adaptation. To test the model, we recorded the responses of single IT cortex neurons to complex visual stimuli while separately adapting the two putative types of input to those neurons. We compared the changes in responses of these neurons following such adaptation with predictions derived from the divisive normalization model. As predicted by the model, we show that adaptation in the IT cortex can, depending on the relative strength of each putative type of input to a neuron, suppress or enhance the neural response to a complex stimulus. More generally, our data suggest that adaptation serves to selectively enhance processing of the stimuli that differ from recently experienced ones, even when these occur within a configuration of multiple stimuli. SIGNIFICANCE STATEMENT Stimulus repetition alters neural responses to the repeated stimulus. This so-called adaptation phenomenon has been robustly demonstrated in brains of different species and is considered to be a form of short-term plasticity inherent to the processing of sensory stimuli. Nevertheless, the functional role and underlying mechanisms of adaptation remain unclear. Here we demonstrate that divisive normalization, a canonical neural computation operating throughout the brain, predicts the adaptation-induced changes in response of single neurons to complex stimulus configurations in the macaque inferotemporal cortex. Our findings embed adaptation effects of inferotemporal neurons into the context of a broader neural network perspective that includes divisive normalization. Additionally, our findings have implications for understanding of the function of adaptation in higher-order sensory cortices.
Architecture and migration of an epithelium on a cylindrical wire

Significance Cell sheets often organize in tubular structures, for example, in the kidney. Also, cells from epithelial tumors are known to wrap around vessels or muscle fibers as they migrate collectively. By plating cells on thin glass wires, we mimic these physiological conditions in vitro and show that high curvature favors cell detachment at the front edge. This switch from collective to individual migration may reproduce features often observed in cancer invasion. High curvature also induces a circumferential organization of the actin cytoskeleton reminiscent of in vivo embryonic morphogenesis situations where tissues develop on a cylindrical template. Finally, monolayer migration is halted at submicron radii, and the tissue reconfigures into hollow cysts at its leading tip. In a wide range of epithelial tissues such as kidney tubules or breast acini, cells organize into bidimensional monolayers experiencing an out-of-plane curvature. Cancer cells can also migrate collectively from epithelial tumors by wrapping around vessels or muscle fibers. However, in vitro experiments dealing with epithelia are mostly performed on flat substrates, neglecting this out-of-plane component. In this paper, we study the development and migration of epithelial tissues on glass wires of well-defined radii varying from less than 1 µm up to 85 µm. To uncouple the effect of out-of-plane curvature from the lateral confinement experienced by the cells in these geometries, we compare our results to experiments performed on narrow adhesive tracks. Because of lateral confinement, the velocity of collective migration increases for radii smaller than typically 20 µm. The monolayer dynamics is then controlled by front-edge protrusions. Conversely, high curvature is identified as the inducer of frequent cell detachments at the front edge, a phenotype reminiscent of the Epithelial−Mesenchymal Transition. High curvature also induces a circumferential alignment of the actin cytoskeleton, stabilized by multiple focal adhesions. This organization of the cytoskeleton is reminiscent of in vivo situations such as the development of the trachea of the Drosophila embryo. Finally, submicron radii halt the monolayer, which then reconfigures into hollow cysts.
Chimeric Trop2 Virus-like Particles: A Potential Immunotherapeutic Approach Against Pancreatic Cancer

Trop2 is a recently discovered cell surface glycoprotein overexpressed in pancreatic cancer which could potentially be used as an immunotherapeutic target. Enveloped virus-like particles (VLPs) are highly immunogenic and versatile immune stimulatory agents which can be modified to incorporate exogenous proteins on their membrane envelope to use as cancer vaccines. In this study, we investigated the effects of murine Trop2 (mTrop2) VLP immunization in a pancreatic cancer syngeneic murine model. VLPs incorporating mTrop2 were used to immunize C57BL/6 tumor-bearing mice. Immunization with mTrop2 VLPs led to a significant reduction in tumor growth accompanied by a broad activation and tumor infiltration of CD4+ and CD8+ T cells as well as natural killer and natural killer T cells. VLP immunization generated mTrop2-specific cytotoxic T lymphocytes and antibodies with no measurable induction of autoimmunity. Importantly, VLP immunization decreased the population of regulatory T cells and myeloid-derived suppressor cells inside the tumor tissue resulting in decreased levels of immunosuppressive cytokines like interleukin-10 and transforming growth factor-&bgr; while promoting the activation of immature macrophages and dendritic cells. Furthermore, combination of VLP immunization with gemcitabine treatment showed an improved effect significantly increasing the survival of tumor bearing mice. Our results demonstrate that mTrop2 VLP immunization can activate broad antitumor immune responses and affect key players in the tumor microenvironment overcoming a major barrier, which has limited the efficacy of cancer vaccines. This study presents a novel immunotherapeutic approach which could potentially be used as an alternative treatment option in combination therapies to treat pancreatic cancer patients.
Identifying Patients With Ischemic Heart Disease in an Electronic Medical Record

Purpose: Increasing utilization of electronic medical records (EMRs) presents an opportunity to efficiently measure quality indicators in primary care. Achieving this goal requires the development of accurate patient-disease registries. This study aimed to develop and validate an algorithm for identifying patients with ischemic heart disease (IHD) within the EMR. Methods: An algorithm was developed to search the unstructured text within the medical history fields in the EMR for IHD-related terminology. This algorithm was applied to a 5% random sample of adult patient charts (n = 969) drawn from a convenience sample of 17 Ontario family physicians. The accuracy of the algorithm for identifying patients with IHD was compared to the results of 3 trained chart abstractors. Results: The manual chart abstraction identified 87 patients with IHD in the random sample (prevalence = 8.98%). The accuracy of the algorithm for identifying patients with IHD was as follows: sensitivity = 72.4% (95% confidence interval [CI]: 61.8-81.5); specificity = 99.3% (95% CI: 98.5-99.8); positive predictive value = 91.3% (95% CI: 82.0-96.7); negative predictive value = 97.3 (95% CI: 96.1-98.3); and kappa = 0.79 (95% CI: 0.72-0.86). Conclusions: Patients with IHD can be accurately identified by applying a search algorithm for the medical history fields in the EMR of primary care providers who were not using standardized approaches to code diagnoses. The accuracy compares favorably to other methods for identifying patients with IHD. The results of this study may aid policy makers, researchers, and clinicians to develop registries and to examine quality indicators for IHD in primary care.
Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy

Serum cystatin C is believed to reflect the glomerular filtration rate (GFR) more closely than serum creatinine in many contexts and a reference interval for serum cystatin C in term pregnancy has been defined to enable its use also in pregnant women. However, serum cystatin C levels were not found to be decreased in term pregnancy, though GFR of low molecular mass substances is known to increase by at least 40% by the third trimester. The aim of this study was therefore to determine whether serum cystatin C is a reliable GFR marker also in pregnant women. GFR was determined by measurement of plasma clearance of iohexol in 48 previously healthy women in their third trimester and in 12 healthy nonpregnant women, and was compared with their serum levels of cystatin C and creatinine. Both serum cystatin C and creatinine levels were significantly related to GFR for both pregnant and non-pregnant women. However, the correlation between cystatin C and GFR was set at different levels for pregnant and nonpregnant women. Our results indicate a physiological difference between the filtration processes in kidneys of pregnant and non-pregnant women, whether it is size-dependent, configuration-dependent or charge-dependent. Nevertheless, serum cystatin C seems to reflect GFR reliably in both non-pregnant and pregnant, healthy and hypertensive women.
Both aerobic exercise and cognitive-behavioral therapy reduce chronic fatigue in FSHD

Objective: To investigate the effect of aerobic exercise training (AET) and cognitive-behavioral therapy (CBT) on chronic fatigue in patients with facioscapulohumeral muscular dystrophy (FSHD). Methods: We performed a multicenter, assessor-blinded, randomized clinical trial (RCT). Fifty-seven patients with FSHD type 1 with severe chronic fatigue were randomly allocated to AET, CBT, or usual care (UC). Outcomes were assessed before treatment, following 16 weeks of intervention, and after a 12-week follow-up. A linear mixed model for repeated measurements was used to study the estimated group differences. Results: Following treatment, both the AET (28 participants) and CBT (25 participants) intervention groups had less fatigue relative to the UC group (24 participants), with a difference of −9.1 for AET (95% confidence interval [CI] −12.4 to −5.8) and −13.3 for CBT (95% CI −16.5 to −10.2). These beneficial effects lasted through follow-up, with a difference of −8.2 for AET (95% CI −12.4 to −5.8) and −10.2 for CBT (95% CI −14.0 to −6.3). The patients who received CBT had an increase in registered and experienced physical activity, sleep quality, and social participation. The patients who received AET had an increase in registered physical activity only. The increase in registered physical activity in both groups and the improvement in social participation following CBT were still present at follow-up. Conclusions: This RCT shows that AET and CBT can ameliorate chronic fatigue in patients with FSHD. Classification of evidence: This study provides Class III evidence that, in patients with FSHD type 1 and severe chronic fatigue, AET or CBT reduces the severity of chronic fatigue.
Insertion of the F Factor into the Cluster of rfa (Rough A) Genes of Salmonella typhimurium

From F+ strains of Salmonella typhimurium, isolates were obtained representing two new classes of Hfr strains, HfrK1 and HfrK2, in which the insertion of the F factor into the rfa genes results in chromosome mobilization either clockwise or anticlockwise from rfa, and in the Rfa phenotype. The point of insertion of the F factor into the cluster of rfa genes, revealed by studies of the early transfer of their normal alleles, is as follows: xyl-cysE-rfa-657 (HfrK2-1, SA540 →)–(← HfrK1-1, SA458)–rfaG-(← HfrK1-2, SA464)–pyrE-metA
Non-HLA antibodies in transplantation: when do they matter?

Purpose of reviewA growing interest in the contribution of non-human leukocyte antigens (non-HLA) antibodies to allograft rejection has led to the identification of multiple target antigens and investigation into the possible mechanisms of injury. Although several non-HLA antibody specificities have been identified, the largest cohorts studied are those detected using commercial assays. This review focuses on the phenotypes of injury associated with non-HLA antibody and defines in-vivo environmental characteristics that may be conducive to non-HLA antibody-mediated injury. Recent findingsMechanistic studies in animal models and clinical data suggest that an inflammatory environment, increased antigen expression, and development of neoantigens through posttranslational modifications contribute to non-HLA antibody development and their subsequent contribution to allograft injury. Furthermore, many reports show worse outcomes when HLA and non-HLA antibodies are present, suggesting possible interactions between these antibodies that lead to increased injury. Plasmapheresis and intravenous immunoglobulin are currently used to reduce HLA and non-HLA antibodies; however, therapeutic strategies targeting B cells and plasma cells simultaneously may lead to more durable antibody elimination. SummaryImmune triggers that lead to non-HLA antibody formation are complex and poorly understood. The ability of non-HLA antibodies to mediate allograft injury may depend upon their specificity and affinity, density of the target antigen, and synergy with HLA antibodies.
Survey of Hand and Upper Extremity Injuries Among Rock Climbers

Background: Rock climbing first evolved as a sport in the late 18th century. With its growing popularity, the number of rock climbing–related injuries has potential to increase, spurring a rise in the number of articles associated with it. Despite the available literature, there remains a paucity of information about upper extremity injuries sustained by rock climbers, and no studies to date have focused on gender-specific injuries. Methods: A 24-question online survey was distributed to rock climbers about upper extremity injuries sustained during rock climbing. Statistical analysis was used to study association between participants’ demographics and injuries. Results: A total of 397 participants responded to the survey. Mean age was 32.5 years with males comprising 85%. No significant differences in demographics or climbing behaviors were found between males and females. Ninety percent of participants reported sustaining an upper extremity injury. Fingers were the most common injury followed by shoulder/arm and elbow/forearm. Our study found females to be more likely to report a rock climbing–related injury, and more likely to undergo surgery for it. Conclusion: Female rock climbers were significantly more likely to report a shoulder/upper arm injury and were also more likely to report undergoing surgery compared with males, where these differences were not due to age or climbing behaviors. Further investigation is warranted into the association between shoulder injuries and female athletes to determine how the gender differences relate to extent of injury as well as health service utilization behaviors.
Alteration of SLP2‐like immunolabeling in mitochondria signifies early cellular damage in developing and adult mouse brain

Mitochondria play a critical role in various pathways of regulated cell death. Here we propose a novel method for detection of initial derangement of mitochondria in degenerating and dying neuronal cells. The method is based on our recent finding that antibodies directed against the cannabinoid type 1 receptor (CB1) also bind the mitochondrial stomatin‐like protein 2 (SLP2) that belongs to an inner mitochondrial membrane protein complex. It is well established that SLP2 regulates mitochondrial biogenesis and respiratory functions. We now show that anti‐CB1 antibodies recognize conformational epitopes but not the linear amino acid sequence of SLP2. In addition we found that anti‐CB1 serum mostly labels swollen mitochondria with early or advanced stages of pathology in mouse brain while other proteins of the complex may mask epitopes of SLP2 in the normal mitochondria. Although neurons and endothelial cells in healthy brains contain occasional immunopositive mitochondria detectable with anti‐CB1 serum, their numbers increase significantly after hypoxic insults in parallel with signs of cellular damage. Moreover, use of electron microscopy suggests relocation of SLP2 from its normal functional position in the inner mitochondrial membrane into the mitochondrial matrix in pathological cells. Thus, SLP2‐like immunolabeling serves as an in situ histochemical target detecting early derangement of mitochondria. Anti‐CB1 serum is crucial for this purpose because available anti‐SLP2 antibodies do not provide selective labeling of mitochondria in the fixed tissue. This new method of detecting mitochondrial dysfunction can benefit the in vitro research of human diseases and developmental disorders by enabling analysis in live animal models.
Can presence of oral Fordyce's granules serve as a marker for hyperlipidemia?

Background: Hyperlipidemia is a well-documented risk factor for coronary heart disease and a great wealth of clinical trials have shown that early detection of hyperlipidemia and prescribing drugs that lower elevated lipid levels reduce serious cardiovascular events, such as myocardial infarction, heart failure and stroke. Fordyce granules (FGs) are sebaceous glands without hair follicles, most often located under the epithelium of the cheek and the vermilion border of lip. The incidence of FGs is typically high and their presence is usually regarded as a normal variation of the oral mucosa. The aim of this study was to investigate the pattern of anatomical distribution and density of FGs and also to explore any potential relationship between the detection of FGs and the state of hyperlipidemia. Materials and Methods: A cross-sectional, prospective study was designed. The participants were divided into two groups; first group consisted of individuals with FGs and the second group included those with no FGs detected. All participants were fasting 9-12 h before they were subjected to a comprehensive oral examination and their blood was sampled and tested for complete lipid profile. The presence of FGs was scored based on the number of the granules and their anatomical distribution. Chi-square test was used and P < 0.05 was considered as significant. Results: A total of 350 patients were recruited for this study, nearly 90% (n = 314) elicit detectable FGs. The FGs were mainly located on the buccal mucosa with or without labial involvement and their density tend to reduce with age and also with smoking. Individuals with elevated lipid profile tend to have the highest score of the FGs. Conclusion: According to this report, the presence of high numbers of FGs in people with high risk factors for cardiovascular disease should not be neglected.
An interdisciplinary treatment approach combining orthodontic forced eruption with immediate implant placement to achieve a satisfactory treatment outcome: a case report.

BACKGROUND Periodontal disease often results in severely bony defects around the teeth and leads to eventual extraction. Remaining bone morphology often compromises ideally restoration-driven positions and deteriorates the success rates for dental implants. PURPOSE The present investigation illustrates the clinical outcome of immediately installing an implant following orthodontic forced eruption and atraumatic extraction. MATERIAL AND METHODS The subject of this study is a 40-year-old Asian female with a right mandibular first molar that had a deep probing depth on the mesial side and mobility. Via the aid of radiographic examination, the tooth that had an angular bony defect and apical lesion was diagnosed as having deep caries and chronic periodontitis with a poor prognosis. After consultation with the patient, we developed a treatment plan incorporating a forced eruption with immediate implantation, intended to augment the alveolar bone volume and increase the width of keratinized gingivae, in a nonsurgical manner. RESULTS Following 12 months of orthodontic treatment, the tooth was successfully moved occlusally in conjunction with an 8 mm vertical interdental bone augmentation. Because of sufficient volume of bone and satisfactory gingival dimensions, the implant showed adequate initial stability in the correct position to facilitate physiological and aesthetic prerequisites. After 6 months of osteointegration, a customized impression coping was utilized to transfer the established emergence profile to a definitive cast for the fabrication of a customized abutment. The final prosthesis was made using a customized metal abutment and ceramometal crown. CONCLUSION In the face of difficult clinical challenges, meticulous inspection and a comprehensive treatment plan were crucial. Interdisciplinary treatment through the careful integration of multiple specialists suggests the possibility of optimal results with high predictability.
Effect of developmental and ancestral high-altitude exposure on VO(2)peak of Andean and European/North American natives.

Peak oxygen consumption (VO(2)peak) was measured in 150 adult males (18-35 years old) in Bolivia, using a complete migrant study design to partition developmental from ancestral (genetic) effects of high-altitude (HA) exposure. High-altitude natives (HANs, Aymara/Quechua ancestry, n = 75) and low-altitude natives (LANs, European/North American ancestry, n = 75) were studied at high altitude (3,600-3,850 m) and near sea level (420 m). HAN and LAN migrant groups to a nonnative environment were classified as: multigeneration migrants, born and raised in a nonnative environment; child migrants who migrated to the nonnative environment during the period of growth and development (0-18 years old); and adult migrants who migrated after 18 years of age. Variability in VO(2)peak due to high-altitude adaptation was modeled by covariance analysis, adjusting for fat-free mass and physical activity (training) differences between groups. A trend for increased VO(2)peak with increasing developmental high-altitude exposure in migrant groups did not reach statistical significance, but low statistical power may have limited the ability to detect this effect. HANs and LANs born, raised, and tested at high altitude had similar VO(2)peak values, indicating no genetic effect, or an effect much smaller than that reported previously in the literature. There was no functional correlation between forced vital capacity and VO(2)peak, within or across groups. These results do not support the hypothesis that Andean HANs have been selected to express a greater physical work capacity in hypoxia.