Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive side-effects of electroconvulsive therapy: what are they, how to monitor them and what to tell patients

Background Electroconvulsive therapy (ECT) is recommended in treatment guidelines as an efficacious therapy for treatment-resistant depression. However, it has been associated with loss of autobiographical memory and short-term reduction in new learning. Aims To provide clinically useful guidelines to aid clinicians in informing patients regarding the cognitive side-effects of ECT and in monitoring these during a course of ECT, using complex data. Method A Committee of clinical and academic experts from Australia and New Zealand met to the discuss the key issues pertaining to ECT and cognitive side-effects. Evidence regarding cognitive side-effects was reviewed, as was the limited evidence regarding how to monitor them. Both issues were supplemented by the clinical experience of the authors. Results Meta-analyses suggest that new learning is impaired immediately following ECT but that group mean scores return at least to baseline by 14 days after ECT. Other cognitive functions are generally unaffected. However, the finding of a mean score that is not reduced from baseline cannot be taken to indicate that impairment, particularly of new learning, cannot occur in individuals, particularly those who are at greater risk. Therefore, monitoring is still important. Evidence suggests that ECT does cause deficits in autobiographical memory. The evidence for schedules of testing to monitor cognitive side-effects is currently limited. We therefore make practical recommendations based on clinical experience. Conclusions Despite modern ECT techniques, cognitive side-effects remain an important issue, although their nature and degree remains to be clarified fully. In these circumstances it is useful for clinicians to have guidance regarding what to tell patients and how to monitor these side-effects clinically.
Civil disobedience in scientific authorship: Resistance and insubordination in science

ABSTRACT The distribution of credit, resources and opportunities in science is heavily skewed due to unjust practices and incentives, hardwired into science’s rules, guidelines and conventions. A form of resistance widely available is to break those rules. We review instances of rule-breaking in scientific authorship to allow for a redefinition of the concept of civil disobedience in the context of academic research, as well as the conditions on which the label applies. We show that, in contrast to whistleblowing or conscientious objection, civil disobedience targets science’s injustice on a more systemic level. Its further development will ease critical evaluation of deviant actions as well as helping us evaluate deviance, defiance and discontent in science beyond issues of authorship. However, empirically, civil disobedience in science engenders uncertainties and disagreements on the local status of both act and label.
The entanglement between flaviviruses and ER-shaping proteins

The endoplasmic reticulum (ER) is a continuous intracellular membrane system that composes the nuclear envelope and radiates out to the peripheries of the cell, transitioning from ribosome-studded, flat cisternal sheets to highly curved reticulated tubules. It has been implicated in a diverse array of cellular functions, including production, trafficking, and degradation of proteins; synthesis and distribution of lipids and steroids; calcium sequestration and release; cell signaling and innate immunity; carbohydrate metabolism; and detoxification of harmful substances [1]. Such a ubiquitous and functionally versatile organelle is parasitized by viruses in order to facilitate their life cycle. Rotavirus, vaccinia virus (VV), hepatitis C virus (HCV), as well as members of the Flavivirus genus—dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and Zika virus (ZIKV)—are all intimately associated with the ER [2]. The flaviviruses replicate on the ER membranes and form immature viral particles that bud into the ER lumen. These particles are then trafficked through the ER–Golgi network and undergo a maturation process brought about by pH alteration and cleavage by the hostprotease Furin. This viral takeover of the ER requires the co-opting of cellular proteins as well as the active remodeling of the ER membrane to create a cellular environment more conducive to replication [3]. Several ER proteins have been identified as host factors in flavivirus replication [4], but a class of resident proteins that shape and maintain the dynamic ER architecture are of particular interest. These “ER-shaping” proteins could potentially serve as host factors that support viral replication or restriction factors that protect the ER. Interactome and CRISPR screens have produced somewhat discordant results, but the less stringent screens suggest that ER-shaping proteins may be targets of viral proteins [5] [6] [7]. This Pearl review will explore the virus-induced ER-membrane rearrangement and the relationship between ER-shaping proteins and the flavivirus life cycle.
Application of Selected Muscle Strength and Body Mass Cut-Points for the Diagnosis of Sarcopenia in Men and Women with or at risk for HIV Infection.

BACKGROUND Persons with HIV may experience greater mobility limitations than uninfected populations. Accurate tools are needed to identify persons at greatest risk of decline. We evaluated the performance of novel muscle weakness metrics (grip, grip/body mass index [BMI], grip/weight, grip/total body fat, grip/arm lean mass) and association with slowness and falls in older persons with or at risk for HIV infection as part of the work of the Sarcopenia Definitions and Outcomes Consortium (SDOC). METHODS We assessed the prevalence of sarcopenia among 398 men (200 HIV+, 198 HIV-) from the Multicenter AIDS Cohort Study and 247 women (162 HIV+, 85 HIV-) from the Women's Interagency HIV Study using previously validated muscle weakness metrics discriminative of slowness. Sensitivity and specificity were used to compare new muscle weakness and slowness criteria to previously proposed sarcopenia definitions. RESULTS The prevalence of muscle weakness ranged from 16-66% among men and 0-47% among women. Grip/BMI was associated with slowness among men with HIV only. Grip/BMI had low sensitivity (25-30%) with moderate to high specificity (68-89%) for discriminating of slowness; all proposed metrics had poor performance in the discrimination of slowness (AUC <0.62) or fall status (AUC <0.56). The combination of muscle weakness and slowness was not significantly associated with falls (p ≥0.36), with a low sensitivity in identifying those sustaining one or more falls (sensitivity ≤16%). DISCUSSION Clinical utility of new sarcopenia metrics for identification of slowness or falls in men and women with or at risk for HIV is limited, given their low sensitivity.
Sexual function in German women with systemic sclerosis compared to women with systemic lupus erythematosus and evaluation of a screening test.

OBJECTIVES To assess and compare sexual dysfunction (SDF) in female patients with systemic sclerosis (SSc) or systemic lupus erythematosus (SLE), to correlate sexual function with disease characteristics and depression, and to evaluate a short questionnaire (Qualisex) as a screening test. METHODS Female patients with systemic sclerosis or systemic lupus erythematosus in two German tertiary university hospitals were evaluated in a prospective study. A self-designed questionnaire, the Female Sexual Function Index (FSFI), the Qualisex, and the Beck's depression inventory were used. RESULTS 171 female patients were included into the study (83 with SSc, and 88 with SLE). 62.6% (52 of 83) of SSc patients and 67.0% (59 of 88) of SLE patients were sexually active. Only 9.6% of SSc patients and 14.8% of SLE patients had ever discussed sexual problems with their physician. Significantly more SSc patients would wish to discuss sexuality with their physician more intensively (37.3% vs. 28.4% in SLE patients, p=0.011). Among the 51 sexually active and evaluable SSc patients a mean FSFI of 25.53 (±5.06) was found, with a FSFI value defining sexual dysfunction (SDF) (<26.55) in 49% of patients, which did not differ significantly compared to SLE patients (n=59, mean FSFI 26.92 (±5.17), SDF in 45.8%). The Qualisex correlated significantly with the FSFI, and both Qualisex and FSFI correlated with depressiveness. CONCLUSIONS Sexual dysfunction (SDF) is a frequent problem in female patients with SSc and SLE. Addressing sexual issues during medical consultation is an unmet need. The Qualisex constitutes a short questionnaire, which is suitable for addressing concerns on sexuality.
Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma

Purpose: A persistent issue in cancer drug development is the discordance between robust antitumor drug activity observed in laboratory models and the limited benefit frequently observed when patients are treated with the same agents in clinical trials. Difficulties in accurately modeling the complexities of human tumors may underlie this problem. To address this issue, we developed Comparative In Vivo Oncology (CIVO), which enables in situ investigation of multiple microdosed drugs simultaneously in a patient's tumor. This study was designed to test CIVO's safety and feasibility in patients with soft tissue sarcoma (STS). Patients and Methods: We conducted a single arm, prospective, 13-patient pilot study. Patients scheduled for incisional biopsy or tumor resection were CIVO-injected 1 to 3 days prior to surgery. Saline or microdoses of anticancer agents were percutaneously injected into the tumor in a columnar fashion through each of eight needles. Following excision, drug responses were evaluated in the injected tissue. Results: The primary objective was met, establishing CIVO's feasibility and safety. Device-related adverse events were limited to transient grade 1 nonserious events. In addition, biomarker evaluation of localized tumor response to CIVO microinjected drugs by IHC or with NanoString GeoMx Digital Spatial Profiler demonstrated consistency with known mechanisms of action of each drug, impact on the tumor microenvironment, and historic clinical activity. Conclusions: These results are an advance toward use of CIVO as a translational research tool for early evaluation of investigational agents and drug combinations in a novel approach to phase 0 trials. See related commentary by Sleijfer and Lolkema, p. 3897
Neuromuscular Blockers in Acute Respiratory Distress Syndrome: Flat Dose or Not. Are We Missing the Point?

e438 www.ccmjournal. org May 2020 • Volume 48 • Number 5 2. Lederer DJ, Bell SC, Branson RD, et al: Control of confounding and reporting of results in causal inference studies. Guidance for authors from editors of respiratory, sleep, and critical care journals. Ann Am Thorac Soc 2019; 16:22–28 3. Zhang Z: Model building strategy for logistic regression: Purposeful selection. Ann Transl Med 2016; 4:111 4. Gayat E, Pirracchio R, Resche-Rigon M, et al: Propensity scores in intensive care and anaesthesiology literature: A systematic review. Intensive Care Med 2010; 36:1993–2003 5. Zhang Z: Propensity score method: A non-parametric technique to reduce model dependence. Ann Transl Med 2017; 5:7 DOI: 10.1097/CCM.0000000000004274
Low anterior resection syndrome after right‐ and left‐sided resections for colonic cancer

This population‐based cohort study aimed to evaluate occurrence of low anterior resection syndrome (LARS) and correlate this to health‐related quality of life in patients who had undergone segmental colonic resection for colonic cancer in the Stockholm–Gotland region. The hypothesis was that there is a difference in occurrence of LARS depending on whether a right‐ or a left‐sided resection was performed.
The spatial relation of diabetic retinal neurodegeneration with diabetic retinopathy

Purpose Diabetic retinal neurodegeneration (DRN) has been demonstrated in eyes of patients with diabetes mellitus (DM), even in the absence of diabetic retinopathy (DR). However, no studies have looked at the rate of change in retinal layers and presence/development of DR over time per quadrant of the macula. In this longitudinal study, we aimed to clarify whether the rate of DRN is associated with the development/presence of DR within 4 different quadrants of the retina. Methods 80 eyes of 40 patients with type 1 DM and no/minimal DR were included. At 4 visits over 6 years, SD-OCT and fundus images were acquired. Thickness of the Retinal Nerve Fiber Layer (RNFL), Ganglion Cell Layer (GCL) and Inner Plexiform Layer (IPL) was measured in a 1-6mm circle around the fovea overall and for each quadrant (superior, nasal, inferior, temporal). Fundus images were scored for the presence/absence of DR in these areas. Multilevel analyses were performed to determine the rate of change for each layer overall and per quadrant for eyes/quadrants without and with DR during the follow-up period. Results RNFL and GCL showed significant thinning over time, IPL significant thickening. These changes were more pronounced for GCL and IPL in eyes/quadrants with DR during the follow-up period. Conclusions RNFL and GCL both showed thinning over time, which was more pronounced in eyes with DR for GCL. This holds true even in regional parts of the retina, as quadrant analyses showed similar results, showing that structural DRN is associated with DR per quadrant independently.
Screw Removal Can Resolve Unexplained Anterior Pain Without Recurrence of Shoulder Instability After Open Latarjet Procedures

Background: Anterior shoulder instability can be successfully treated using Latarjet procedures, although a small proportion of patients report unexplained pain. Purpose/Hypothesis: The purpose was to report the prevalence and characteristics of patients with unexplained pain without recurrent instability after open Latarjet procedures and to determine whether screw removal can alleviate pain. The hypothesis was that unexplained pain without recurrent instability might be due to soft tissue impingements against the screw heads and that the removal of screws would alleviate or reduce pain. Study Design: Case series; Level of evidence, 4. Methods: We retrospectively reviewed the clinical and radiographic records of 461 consecutive shoulders treated by open Latarjet procedures for anterior instability between 2002 and 2014. Unexplained anterior pain was present in 21 shoulders (4.6%) and treated by screw removal at 29 ± 37 months (mean ± SD). Postoperative assessment at >12 months after screw removal included complications, visual analog scale for pain (pVAS), subjective shoulder value, Rowe score, Walch-Duplay score, and ranges of motion. The study cohort comprised the shoulders of 20 patients (9 women, 11 men) aged 25 ± 6 years (median, 25 years; range, 16-34 years) at screw removal and involved the dominant arm in 13 (62%) shoulders. Results: Screw removal alleviated pain completely in 14 shoulders (67%; pVAS improvement, 6.4 ± 1.8; median, 6; range, 3-8) and reduced pain in the remaining 7 (33%; pVAS improvement, 2.4 ± 1.4; median, 2; range, 1-5). At 38 ± 23 months after screw removal, 2 recurrences of instability unrelated to screw removal occurred. The subjective shoulder value was 79% ± 22% (median, 90%; range, 0%-95%); Rowe score, 85 ± 20 (median, 95; range, 30-100); and Walch-Duplay score, 82 ± 19 (median, 85; range, 25-100). Mobility improved in active forward elevation (171°± 14°), external rotation with the elbow at the side (61°± 12°), and external rotation with the arm at 90° of abduction (67°± 13°) and especially in internal rotation, with only 2 shoulders (10%) limited to T12 spine segment. Conclusion: The present findings confirm that unexplained anterior pain after Latarjet procedures can be related to the screws used to fix bone blocks, which can safely be alleviated or reduced by screw removal.
Changes in countermovement jump performance and subjective readiness-to-train scores following a simulated soccer match

Abstract The study investigated whether countermovement jump (CMJ) metrics and subjective responses to a readiness-to-train questionnaire (RTT-Q) tracked simulated match-induced acute fatigue. This was a randomized cross-over repeated measures study. Participants were assigned into one of two groups; CONTROL or LIST. The LIST group performed the Loughborough Intermittent Shuttle Run (LIST), which was designed to simulate the demands of a soccer match. The CONTROL performed light physical activity at an intensity of <65% of maximal heart rate. Each group performed three CMJ’s and completed an RTT-Q before (PRE), and again at 24 and 48 h after the LIST and/or CONTROL interventions. At 24 h there were significant differences in RTT-Q answers between the Pre and 24 h for the LIST group for questions; “Do you feel physically strong today? ” and “Do you have muscle soreness today? ” (p = 0.02 and 0.0008, respectively). The questions “Do you feel mentally strong today? ” and “Do you have muscle soreness today? ” (p = 0.02 and p = 0.0001 respectively) were the only questions that had a significant difference between Pre and 48 h for the LIST group. None of the CMJ metrics (LIST or CONTROL) changed significantly at any stage of the experiment. Although fatigue was detected by changes in the RTT-Q at 24 and 48 h after the LIST, none of the CMJ metrics changed. These findings suggest that subjective measures are more sensitive to low-level fatigue than objective measures, thus effective monitoring should include both.
Drug selection for sedation and general anesthesia in children undergoing ambulatory magnetic resonance imaging

The demand for drug-induced sedation for magnetic resonance imaging (MRI) scans have substantially increased in response to increases in MRI utilization and growing interest in anxiety in children. Understanding the pharmacologic options for deep sedation and general anesthesia in an MRI environment is essential to achieve immobility for the successful completion of the procedure and ensure rapid and safe discharge of children undergoing ambulatory MRI. For painless diagnostic MRI, a single sedative/anesthetic agent without analgesia is safer than a combination of multiple sedatives. The traditional drugs, such as chloral hydrate, pentobarbital, midazolam, and ketamine, are still used due to the ease of administration despite low sedation success rate, prolonged recovery, and significant adverse events. Currently, dexmedetomidine, with respiratory drive preservation, and propofol, with high effectiveness and rapid recovery, are preferred for children undergoing ambulatory MRI. General anesthesia using propofol or sevoflurane can also provide predictable rapid time to readiness and scan times in infants or children with comorbidities. The selection of appropriate drugs as well as sufficient monitoring equipment are vital for effective and safe sedation and anesthesia for ambulatory pediatric MRI.
Impact of weight loss achieved with laparoscopic sleeve gastrectomy on early markers of atherosclerotic vascular disease: a prospective study.

BACKGROUND Considering the emerging role of the aortic propagation velocity (APV) in the determination of the coronary artery disease (CAD) burden, we hypothesized that laparoscopic sleeve gastrectomy (LSG) could provide improvement in APV in morbidly obese subjects Aims: This study purposed to investigate the impact of LSG on surrogate markers of the atherosclerotic vascular disease such as APV, carotid intima-media thickness (CIMT), epicardial fat thickness (EFT) and ankle-brachial index (ABI) in subjects with morbid obesity. METHODS Seventy-one subjects who were scheduled for LSG for standard indications stated by the international guidelines were prospectively enrolled in the study. All subjects underwent transthoracic echocardiography, carotid ultrasonography. Delta (Δ) values were obtained by subtracting sixth-month values from the baseline values. RESULTS LSG led to a significant reduction in body weight and at postoperative 6 months. There was a significant reduction in systolic and diastolic blood pressure and in triglyceride and LDL cholesterol levels. Moreover, significant reductions in EFT, and CIMT and significant increases in ABI and APV were noted at postoperative six months compared to the baseline measurements. The change in APV was significantly correlated with systolic blood pressure, diastolic blood, EFT, ABI and CIMT. CONCLUSIONS LSG leads to significant improvements in BMI, and CIMT, EFT, ABI, and APV, which are the surrogate markers of atherosclerotic vascular disease, in morbidly obese subjects at postoperative 6 months. The improvement in APV is correlated with the improvement in BMI, CIMT, EFT, and ABI.
Regulation of Tissue Homeostasis by Innate Lymphoid Cells

The barrier surfaces of the lung, intestine and skin are continually exposed to environmental insults, which can result in infection, inflammation and tissue injury when the barriers become disrupted. Epithelial barrier repair requires a balance between promoting beneficial remodeling responses that drive cell proliferation while also acting to limit these responses once homeostasis has been achieved. Failure to either initiate or resolve these reparative responses has detrimental effects, resulting in either loss of tissue integrity and function or promotion of chronic inflammation and fibrosis, as observed in multiple inflammatory diseases of the respiratory and intestinal tracts. While the immune system is integral to maintaining barrier integrity at these mucosal surfaces, the precise cellular and molecular factors that orchestrate restoration of homeostasis following tissue injury are poorly understood. Over the past several years a novel family of immune cells have emerged called innate lymphoid cells (ILCs) that are crucial regulators of immunity and inflammation at barrier sites. However, whether ILCs exist in the respiratory tract and how they may influence immunity, inflammation or tissue homeostasis in the lung was unknown. The data presented in Chapter 2 identify a population of Group 2 ILCs (ILC2s) constitutively present in the respiratory tract of humans and mice and demonstrate a novel function for ILC2s in regulating airway epithelial barrier integrity and tissue homeostasis following influenza virus-induced pulmonary damage. Further, studies in Chapter 3 investigate the nature of the crosstalk between the damaged tissue and ILC2 function, revealing that ILC2s possess a wound healing transcriptional signature and identifying the amphiregulin (AREG)-epidermal growth factor receptor (EGFR) pathway as an essential regulator of airway epithelial repair and host recovery from influenza virus infection. Lastly, Chapter 4 explores the relevance of this pathway in sites outside the lung, uncovering an interleukin (IL)-33-dependent innate immune mechanism of intestinal tissue repair dependent on AREG-EGFR interactions. Collectively, the data presented in this thesis identify an evolutionarily conserved feedback loop in which cytokine cues from damaged epithelia activate innate immune cells to express growth factors essential for the restoration of epithelial function and maintenance of tissue homeostasis at multiple barrier surfaces. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Immunology First Advisor David Artis Second Advisor David M. Allman This dissertation is available at ScholarlyCommons: http://repository.upenn. edu/edissertations/1374