Miracle-dz/UniFAR-FTUs huggingface dataset:
Memory Impairment in Parkinson’s Disease: The Retrieval Versus Associative Deficit Hypothesis Revisited and Reconciled

Objective: Our study explored the retrieval deficit and the associative deficit hypotheses of memory impairments in Parkinson’s disease (PD). The former supports a memory deficit mediated by attention/executive dysfunctions, whereas the latter hypothesizes a hippocampal memory impairment in PD. Method: We studied 31 controls and 34 PD patients classified as PD with normal cognition (PD-NC; n = 18) and PD with mild cognitive impairment (PD-MCI; n= 16). To test the retrieval deficit hypothesis, we measured the performance in encoding, retention, and recognition in verbal and visual domains; to test the associative deficit hypothesis, we used a specific associative binding measure. Using resting-state functional-MRI, we compared the functional connectivity of different hippocampal subfields between PD patients and controls, and we related it to memory performance. Results: Consistently with the retrieval deficit hypothesis, PD-MCI, and PD-NC, were impaired in free recall encoding and retention in comparison to controls, especially in the visual domain. However, as predicted by the associative deficit hypothesis, PD-MCI and, to a lesser extent, PD-NC, showed also significant associative and binding deficits in cued recall. Notably, PD patients compared to controls did not show structural differences, although they had lower connectivity between the anterior hippocampi and the precuneus/superior parietal cortex. Worse performance in memory was associated with a more severe disruption of the hippocampal connectivity. Conclusions: The pervasive pattern of memory impairment in PD supports both hypotheses. The interplay between the hippocampus, related to associative memory deficits, and the precuneus, related to attentional control, provides a neural signature that reconciles them.
Carotid artery stenosis: accuracy of noninvasive tests--individual patient data meta-analysis.

PURPOSE To find clinically relevant estimates of the accuracy of noninvasive imaging-Doppler ultrasonography (US), computed tomographic (CT) angiography, magnetic resonance (MR) angiography, and contrast material-enhanced MR angiography-in diagnosing both severe and moderate symptomatic carotid artery stenosis; to ascertain the effect of prespecified clinical factors and clinical setting on diagnostic accuracy; and to estimate the probability of agreement between two noninvasive tests. MATERIALS AND METHODS Original principal investigators obtained ethics approval for each data set. All data were anonymized. Individual patient data sets (IPDs) for noninvasive imaging tests were used to determine sensitivity, specificity, and agreement between the tests for symptomatic carotid artery stenosis; to compare ipsilateral with contralateral arteries; to compare IPDs with literature estimates; to compare routine audit and research data; and to determine the effect of age and sex on sensitivity and specificity. RESULTS Contrast-enhanced MR angiography was the most accurate (sensitivity, 0.85 [30 of 35]; 95% confidence interval [CI]: 0.69, 0.93; and specificity, 0.85 [67 of 78]; 95% CI: 0.76, 0.92) for 70%-99% symptomatic stenosis. Sensitivity for a 50%-69% stenosis was poor, although data were limited. Sensitivity and specificity were generally lower in the ipsilateral than in the contralateral artery. IPD estimates were lower than literature values. Results of comparison of research with audit-derived data were inconclusive. Neither age nor sex affected accuracy. Agreement was better between two Doppler US tests and between two contrast-enhanced MR angiographic tests than it was between Doppler US and contrast-enhanced MR angiography, except for a 70%-99% symptomatic stenosis. CONCLUSION Primary studies should distinguish ipsilateral from contralateral arteries and carefully describe the patients' characteristics and study environment. The literature overestimates noninvasive imaging accuracy. More data are needed to inform physicians in routine clinical practice.
Disability with Persistent Pain Following an Epidemic of Chikungunya in Rural South India

Objective. We investigated the effects of chronic rheumatic and musculoskeletal symptoms on the functional status of people affected by the chikungunya (CKG) epidemic in the Calicut District, Kerala, South India in 2009. Methods. A cross-sectional house-to-house survey was conducted 18 months after the CKG epidemic to assess functional status of individuals with post-epidemic persistent pain. All respondents over age 15 years with persistent pain fitting the epidemiological case definition were included. Participants’ functional status was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI). Factors affecting severity of HAQ-DI were analyzed by ordinal regression. Results. Of 3869 subjects interviewed, 1195 (34.3%) had a positive history of CHIKV virus infection (epidemiological or confirmed); 36.28% (624/1720) of CKG-affected individuals had persistent pain 18 months post epidemic. Mean age of those affected was 48.22 ± 15.6 years; 23.2% had no disability, while 16.2% had moderate to severe disability on the HAQ-DI. Significant factors affecting severity of disability on HAQ-DI included previous rheumatic musculoskeletal disease (OR 2.27), joint and soft-tissue involvement (OR 3.74), only joint involvement (OR 2.14), female sex (OR 1.44), diet (OR 4.73), and history of joint swelling (OR 1.72). Conclusion. Persistence of pain noted in post-CKG disease resulted in significantly deteriorated functional status of those affected.
A stable engineered human IgG3 antibody with decreased aggregation during antibody expression and low pH stress

Human IgG comprises four subclasses with different biological functions. The IgG3 subclass has a unique character, exhibiting high effector function and Fab arm flexibility. However, it is not used as a therapeutic drug owing to an enhanced susceptibility to proteolysis. Antibody aggregation control is also important for therapeutic antibody development. To date, there have been few reports of IgG3 aggregation during protein expression and the low pH conditions needed for purification and virus inactivation. This study explored the potential of IgG3 antibody for therapeutics using anti‐CD20 IgG3 as a model to investigate aggregate formation. Initially, anti‐CD20 IgG3 antibody showed substantial aggregate formation during expression and low pH treatment. To circumvent this phenomenon, we systematically exchanged IgG3 constant domains with those of IgG1, a stable IgG. IgG3 antibody with the IgG1 CH3 domain exhibited reduced aggregate formation during expression. Differential scanning calorimetric analysis of individual amino acid substitutions revealed that two amino acid mutations in the CH3 domain, N392K and M397V, reduced aggregation and increased CH3 transition temperature. The engineered human IgG3 antibody was further improved by additional mutations of R435H to obtain IgG3KVH to achieve protein A binding and showed similar antigen binding as wild‐type IgG3. IgG3KVH also exhibited high binding activity for FcγRIIIa and C1q. In summary, we have successfully established an engineered human IgG3 antibody with reduced aggregation during bioprocessing, which will contribute to the better design of therapeutic antibodies with high effector function and Fab arm flexibility.
Synthetic hydroxyapatite and its use in bioactive coatings

An approach to solve the limitations of autologous bone grafting procedures in bone injury treatment is to develop bioactive coatings in the implantation system. The objective of this work is to compare the temperature effect on the stability of hydroxyapatite, graphene, and collagen colloidal suspensions to be used as biocompatible and bioactive coatings on a carbon fiber composite surface. Synthesized hydroxyapatite was assessed by X-ray diffraction. Zeta potential at different temperatures was evaluated. Specimens were characterized using scanning electron microscopy and Raman analysis. The results showed that the best hydroxyapatite/graphene ratio was 85/15, while those of the hydroxyapatite/collagen mixtures were 85/15. A hydroxyapatite/graphene/collagen mixture was synthesized based on these results.
Autologous fat transplantation alters gene expression patterns related to inflammation and hypoxia in the irradiated human breast

Radiation‐induced fibrosis, an adverse effect of breast cancer treatment, is associated with functional and cosmetic impairment as well as surgical complications. Clinical reports suggest improvement following autologous fat transplantation, but the mechanisms underlying this effect are unknown. A global gene expression analysis was undertaken to identify genetic pathways dysregulated by radiation and evaluate the impact of autologous fat transplantation on gene expression.
A Retrospective Dosimetric Study of Radiotherapy Patients with Left-Sided Breast Cancer; Patient Selection Criteria for Deep Inspiration Breath Hold Technique

Background: Several studies have investigated cardiac dose reduction when utilizing the deep inspiration breath hold (DIBH) technique in patients undergoing radiotherapy for left-sided breast cancer. This paper aims to recommend potential selection criteria based on a retrospective single institute study of free breathing (FB) and DIBH computed tomography (CT) simulation planning scans. Methods: Dosimetric comparisons were performed retrospectively for 20 patients correlating the dose reduction and patient anatomical factors (anatomical variation of chest shape, chest wall separation, total lung volume (TLV) and others). Results: Paired t-tests demonstrated significant cardiac dose reduction for most patients but not all. Minimal cardiac dose reduction was observed for three patients using their DIBH plan, with one patient receiving a higher dose. Linear regression analysis identified a positive correlation between the patient’s TLV (on the FB CT simulation scan) and the magnitude of dosimetric benefit received (0.4045 R2). Conclusion: The TLV measured on a FB plan could potentially be utilised to predict cardiac exposure and assist with patient selection for DIBH. This is important in resource allocation, as DIBH may be unnecessarily recommended for some patients with little dosimetric benefit.
A Retrospective Study of Chinese-Specific Glabellar Contraction Patterns

BACKGROUND Botulinum toxin has been widely accepted as safe and effective for the treatment of glabellar lines, and previous studies have classified glabellar contraction patterns into 5 categories. OBJECTIVE To classify the glabellar contraction patterns among a large-scale Chinese population and provide a reference for injections in Chinese patients. METHODS Four hundred eighty-nine Chinese subjects who received botulinum toxin for the treatment of glabellar lines were selected for a retrospective photographic analysis of their glabellar contraction patterns. Using 2 separate previously established classification systems, the patterns were analyzed and classified by a panel of certified Chinese dermatologists. RESULTS Two separate classification systems showed different distributions of glabellar contraction patterns among Chinese compared with Caucasians and Koreans. The classifications allowed for identification of the most frequent patterns in Chinese, which were “converging arrows” and “11” pattern, and provided references for identifying the most important muscles. CONCLUSION Both classification systems are applicable to the Chinese population with varying distributions. Because the classification system of de Almeida and colleagues focuses more on the muscles involved in the formation of glabellar lines, the authors' subjects classified according to this system displayed a more balanced distribution among the 5 patterns. This provides an easier reference for dermatologists in daily clinical practice and guiding treatment strategies.
Usutu Virus Isolated from Rodents in Senegal

Usutu virus (USUV) is a Culex-associated mosquito-borne flavivirus of the Flaviviridae family. Since its discovery in 1959, the virus has been isolated from birds, arthropods and humans in Europe and Africa. An increasing number of Usutu virus infections in humans with neurological presentations have been reported. Recently, the virus has been detected in bats and horses, which deviates from the currently proposed enzootic cycle of USUV involving several different avian and mosquito species. Despite this increasing number of viral detections in different mammalian hosts, the existence of a non-avian reservoir remains unresolved. In Kedougou, a tropical region in the southeast corner of Senegal, Usutu virus was detected, isolated and sequenced from five asymptomatic small mammals: Two different rodent species and a single species of shrew. Additional molecular characterization and in vivo growth dynamics showed that these rodents/shrew-derived viruses are closely related to the reference strain (accession number: AF013412) and are as pathogenic as other characterized strains associated with neurological invasions in human. This is the first evidence of Usutu virus isolation from rodents or shrews. Our findings emphasize the need to consider a closer monitoring of terrestrial small mammals in future active surveillance, public health, and epidemiological efforts in response to USUV in both Africa and Europe.
Associations of Parenting Dimensions and Styles With Externalizing Problems of Children and Adolescents: An Updated Meta-Analysis

The present meta-analysis integrates research from 1,435 studies on associations of parenting dimensions and styles with externalizing symptoms in children and adolescents. Parental warmth, behavioral control, autonomy granting, and an authoritative parenting style showed very small to small negative concurrent and longitudinal associations with externalizing problems. In contrast, harsh control, psychological control, authoritarian, permissive, and neglectful parenting were associated with higher levels of externalizing problems. The strongest associations were observed for harsh control and psychological control. Parental warmth, behavioral control, harsh control, psychological control, autonomy granting, authoritative, and permissive parenting predicted change in externalizing problems over time, with associations of externalizing problems with warmth, behavioral control, harsh control, psychological control, and authoritative parenting being bidirectional. Moderating effects of sampling, child’s age, form of externalizing problems, rater of parenting and externalizing problems, quality of measures, and publication status were identified. Implications for future research and practice are discussed.
[The value of lean nystagmus and sitting to supine positioning nystagmus in the diagnosis of horizontal semicircular canal benign paroxysmal positional vertigo].

Objective: To explore the value of 1ean nystagmus and sitting to supine positioning nystagmus in the diagnosis of horizontal semicircular canal benign paroxysmal positional vertigo. Method: One hundred cases of patients with definitive diagnosis of horizontal semicircular canal benign paroxysmal positional vertigo were tested by 1ean nystagmus and sitting to supine positioning nystagmus and supine roll test. The affected side was recorded according to the nystagmus direction. After diagnosis, they were treated with canalith repositioning procedure. The canalith repositioning procedure was made according to the supine roll test result when 1ean nystagmus and sitting to supine positioning nystagmuscannot be induced. Furthermore，the canalith repositioning procedure was made according to the1ean nystagmus and sitting to supine positioning nystagmuswhenthe supine roll test cannot diagnose. The patients with canalolithiasis were randomly divided into two groups when both 1ean nystagmus and sitting to supine positioning nystagmusand the supine roll test can be induced. One group was treated with canalith repositioning procedure based on results of supine roll test and the other group was treated based on the results of1ean nystagmus and sitting to supine positioning nystagmus. The detection rate and diagnostic coincidence rate of 1ean nystagmus and sitting to supine positioning nystagmus were calculated and the shortterm outcome were evaluated one day after treatment. Result: The detection rate of 1ean nystagmus and sitting to supine positioning nystagmus was 83% and the coincidence rate with the roll test was 90.1%，respectively. There was no significant statistical difference between the treatment effect according to lean nystagmus and sitting to supine positioning nystagmus and supine roll test. Conclusion: Lean nystagmus and sitting to supine positioning nystagmus cannot be used alone in the diagnosis ofhorizontal semicircular canal benign paroxysmal positional vertigo. They need to be combined with supine roll test. However, when the supine roll test is difficult to demonstrate the affected side, it can be used as an auxiliary diagnostic method. When the results of 1ean nystagmus and sitting to supine positioning nystagmusand the supine roll test are inconsistent, repeat the test and conduct a comprehensive assessment to avoid missed diagnosis and misdiagnosis. .
Association of COMT gene variability with pain intensity in patients after total hip replacement

Abstract Pain is one of the most interdisciplinary clinical symptoms of a disease. The aim of the study was to evaluate the association of COMT gene polymorphism with pain perception in patients after total hip replacement (THR). The study included 195 patients qualified for surgical treatment (THR) due to osteoarthritis. Patients previously undergoing hip replacement subsequently underwent multimodal pain management therapy, in accordance with the recommendations for treating postoperative pain. The intensity of pain was measured three times at pre-defined time intervals: 1.5, 6 and 12 months after hip replacement, using the visual analogue scale. Single nucleotide polymorphism (SNP) in the COMT gene rs4680: A>G (Val158Met), rs6269: A>G (promoter region), rs4633: C>T (His62His) and rs4818: C>G (Leu136Leu) was genotyped. COMT SNP frequency distribution was analysed. For rs6269 and rs4818, the minor allele was the G allele (38.7 and 38.5%, respectively). It was also observed that rs4633 (T) allele frequency (50%) equalled that of the rs4680 (A) allele (50%). We assessed COMT haplotype frequency in the patients studied. The most frequent haplotype was haplotype M (ATCA) (50%), the rarest haplotype was haplotype R (ATGG), with a frequency of 0.3%. The most frequent diplotype was H/M, which was found in 37.95% of the patients. The frequency of other diplotypes was: M/M–24.10%, H/H–15.90% and L/M–13.33%. The study showed a significant association of rs4818 G allele and equivalent COMT H haplotype with lower sensitivity to pain after hip replacement.
Astrocyte senescence: Evidence and significance

Astrocytes participate in numerous aspects of central nervous system (CNS) physiology ranging from ion balance to metabolism, and disruption of their physiological roles can therefore be a contributor to CNS dysfunction and pathology. Cellular senescence, one of the mechanisms of aging, has been proposed as a central component of the age dependency of neurodegenerative disorders. Cumulative evidence supports an integral role of astrocytes in the initiation and progression of neurodegenerative disease and cognitive decline with aging. The loss of astrocyte function or the gain of neuroinflammatory function as a result of cellular senescence could have profound implications for the aging brain and neurodegenerative disorders, and we propose the term “astrosenescence” to describe this phenotype. This review summarizes the current evidence pertaining to astrocyte senescence from early evidence, in vitro characterization and relationship to age‐related neurodegenerative disease. We discuss the significance of targeting senescent astrocytes as a novel approach toward therapies for age‐associated neurodegenerative disease.
Severity and Variability of Depression Symptoms Predicting Suicide Attempt in High-Risk Individuals.

Importance Predicting suicidal behavior continues to be among the most challenging tasks in psychiatry. Objectives To examine the trajectories of clinical predictors of suicide attempt (specifically, depression symptoms, hopelessness, impulsivity, aggression, impulsive aggression, and irritability) for their ability to predict suicide attempt and to compute a risk score for suicide attempts. Design, Setting, and Participants This is a longitudinal study of the offspring of parents (or probands) with mood disorders who were recruited from inpatient units at Western Psychiatric Institute and Clinic (Pittsburgh) and New York State Psychiatric Institute. Participants were recruited from July 15, 1997, to September 6, 2005, and were followed up through January 21, 2014. Probands and offspring (n = 663) were interviewed at baseline and at yearly follow-ups for 12 years. Lifetime and current psychiatric disorders were assessed, and self-reported questionnaires were administered. Model evaluation used 10-fold cross-validation, which split the entire data set into 10 equal parts, fit the model to 90% of the data (training set), and assessed it on the remaining 10% (test set) and repeated that process 10 times. Preliminary analyses were performed from July 20, 2015, to October 5, 2016. Additional analyses were conducted from July 26, 2017, to July 24, 2018. Main Outcomes and Measures The broad definition of suicide attempt included actual, interrupted, and aborted attempts as well as suicidal ideation that prompted emergency referrals during the study. The narrow definition referred to actual attempt only. Results The sample of offspring (n = 663) was almost equally distributed by sex (316 female [47.7%]) and had a mean (SD) age of 23.8 (8.5) years at the time of censored observations. Among the 663 offspring, 71 (10.7%) had suicide attempts over the course of the study. The trajectory of depression symptoms with the highest mean scores and variability over time was the only trajectory to predict suicide attempt (odds ratio [OR], 4.72; 95% CI, 1.47-15.21; P = .01). In addition, we identified the following predictors: younger age (OR, 0.82; 95% CI, 0.74-0.90; P < .001), lifetime history of unipolar disorder (OR, 4.71; 95% CI, 1.63-13.58; P = .004), lifetime history of bipolar disorder (OR, 3.4; 95% CI, 0.96-12.04; P = .06), history of childhood abuse (OR, 2.98; 95% CI, 1.40-6.38; P = .01), and proband actual attempt (OR, 2.24; 95% CI, 1.06-4.75; P = .04). Endorsing a score of 3 or higher on the risk score tool resulted in high sensitivity (87.3%) and moderate specificity (63%; area under the curve = 0.80). Conclusions and Relevance The specific predictors of suicide attempt identified are those that clinicians already assess during routine psychiatric evaluations; monitoring and treating depression symptoms to reduce their severity and fluctuation may attenuate the risk for suicidal behavior.