Miracle-dz/UniFAR-FTUs huggingface dataset:
Depression and suicidality in an Afghan refugee: A case report

We report the case of a young male refugee from Afghanistan who presented after a violent suicide attempt, likely precipitated in part by discrimination and social isolation experienced after immigrating to the United States. Common psychiatric comorbidities associated with immigration from war-torn nations are reviewed with a particular emphasis on how adequate screening and additional resources for vulnerable refugees during and after immigration continues to be an unmet need. Our findings suggest that there is a critical need and additional studies should be conducted, not only to identify at risk refugee populations but also to prevent potentially violent behavior. Our findings also suggest a lack of an optimal screening tool and shed light on the struggles of refugees, particularly those from Afghanistan.
Grandparent-Grandchild Relationships: From Families in Contexts to Families as Contexts

Relationships between grandparents and grandchildren provide an excellent framework for integrating family theory and family methodology. Systematic differences as a function of age, gender, life expectancy, and health as played out through generations suggest some topics are best studied by disentangling variability between and within families. Using data from 1,345 grandchildren (52% girls, mean age 13.69 years, range 9 to 20) reporting on 3,664 grandparents, we compare results obtained from studying grandparent-grandchild relationships individually and at the family level. Results suggest important predictors of relationship quality at the within-subject and between-subject levels. Future research should more carefully integrate each level into theory and design.
Intact recognition of facial expression, gender, and age in patients with impaired recognition of face identity

We conducted a series of experiments to assess the ability to recognize the meaning of facial expressions, gender, and age in four patients with severe impairments of the recognition of facial identity. In three patients the recognition of face identity could be dissociated from that of facial expression, age, and gender. In one, all forms of face recognition were impaired. Thus, a given lesion may preclude one type of recognition but not another. We conclude that (1) the cognitive demands posed by different forms of recognition are met at different processing levels, and (2) different levels depend on different neural substrates.
Rural Clients' Continuity Into Follow-Up Substance Use Disorder Treatment: Impacts of Travel Time, Incentives, and Alerts.

PURPOSE Treatment after discharge from detoxification or residential treatment is associated with improved outcomes. We examined the influence of travel time on continuity into follow-up treatment and whether financial incentives and weekly alerts have a modifying effect. METHODS For a research intervention during October 2013 to December 2015, detoxification and residential substance use disorder treatment programs in Washington State were randomized into 4 groups: potential financial incentives for meeting performance goals, weekly alerts to providers, both interventions, and control. Travel time was used as both a main effect and interacted with other variables to explore its modifying impact on continuity of care in conjunction with incentives or alerts. Continuity was defined as follow-up care occurring within 14 days of discharge from detoxification or residential treatment programs. Travel time was estimated as driving time from clients' home ZIP Code to treatment agency ZIP Code. FINDINGS Travel times to the original treatment agency were in some cases significant with longer travel times predicting lower likelihood of continuity. For detoxification clients, those with longer travel times (over 91 minutes from their residence) are more likely to have timely continuity. Conversely, residential clients with travel times of more than 1 hour are less likely to have timely continuity. Interventions such as alerts or incentives for performance had some mitigating effects on these results. Travel times to the closest agency for potential further treatment were not significant. CONCLUSIONS Among rural clients discharged from detoxification and residential treatment, travel time can be an important factor in predicting timely continuity.
Targeting specificity of nuclear-encoded organelle proteins with a self-assembling split-fluorescent protein toolkit

ABSTRACT A large number of nuclear-encoded proteins are targeted to the organelles of endosymbiotic origin, namely mitochondria and plastids. To determine the targeting specificity of these proteins, fluorescent protein tagging is a popular approach. However, ectopic expression of fluorescent protein fusions commonly results in considerable background signals and often suffers from the large size and robust folding of the reporter protein, which may perturb membrane transport. Among the alternative approaches that have been developed in recent years, the self-assembling split-fluorescent protein (sasplit-FP) technology appears particularly promising to analyze protein targeting specificity in vivo. Here, we improved the sensitivity of this technology and systematically evaluated its utilization to determine protein targeting to plastids and mitochondria. Furthermore, to facilitate high-throughput screening of candidate proteins we developed a Golden Gate-based vector toolkit (PlaMinGo). As a result of these improvements, dual targeting could be detected for a number of proteins that had earlier been characterized as being targeted to a single organelle only. These results were independently confirmed with a plant phenotype complementation approach based on the immutans mutant. This article has an associated First Person interview with the first author of the paper. Summary: Optimization of the self-assembling split-GFP system and the assessment of protein-targeting specificity to endosymbiotic organelles in plant cells, utilizing a Golden Gate-based vector toolkit.
Audio cues enhance mirroring of arm motion when visual cues are scarce

Swing in a crew boat, a good jazz riff, a fluid conversation: these tasks require extracting sensory information about how others flow in order to mimic and respond. To determine what factors influence coordination, we build an environment to manipulate incoming sensory information by combining virtual reality and motion capture. We study how people mirror the motion of a human avatar’s arm as we occlude the avatar. We efficiently map the transition from successful mirroring to failure using Gaussian process regression. Then, we determine the change in behaviour when we introduce audio cues with a frequency proportional to the speed of the avatar’s hand or train individuals with a practice session. Remarkably, audio cues extend the range of successful mirroring to regimes where visual information is sparse. Such cues could facilitate joint coordination when navigating visually occluded environments, improve reaction speed in human–computer interfaces or measure altered physiological states and disease.
Potential involvement of dissociated apoA-I in the ABCA1-dependent cellular lipid release by HDL Published, JLR Papers in Press, January 16, 2004. DOI 10.1194/jlr.M300257-JLR200

Helical apolipoproteins of high density lipoprotein (HDL) remove phospholipid and cholesterol from cells and generate HDL particles being mediated by ATP binding cassette transporter A1 (ABCA1). In murine macrophage cell line RAW264 cells, cAMP induced expression of ABCA1, release of cellular phospholipid and cholesterol by apolipoprotein A-I (apoA-I), and reversible binding of apoA-I to the cell. The apoA-I-dependent lipid release was directly proportional to the cAMP-induced binding of apoA-I, and was inhibited 70% by a monoclonal antibody selective to lipid-free apoA-I, 725-1E2. In contrast, apparent cellular cholesterol release to HDL was substantial even without ABCA1 induction, and it was increased only by 27% after the cAMP treatment. The antibody inhibited this increment by 70%. Lipid-free apoA-II liberated apoA-I from HDL by displacement and thereby markedly expanded the cAMP-induced part of the cholesterol release to the HDL-containing medium, and the antibody inhibited this part also by 70%. Binding experiments of the double-labeled reconstituted HDL showed that cAMP induced reversible binding of apoA-I but not the association of cholesteryl ester with the cells. The effect of the antibody on the cellular cholesterol release to the reconstituted HDL was similar to that of the HDL-mediated release. The data implicated that the ABCA1-dependent cholesterol release to HDL is mediated by apoA-I dissociated from HDL.
Plasticity and Potency of Mammary Stem Cell Subsets During Mammary Gland Development

It is now widely believed that mammary epithelial cell plasticity, an important physiological process during the stages of mammary gland development, is exploited by the malignant cells for their successful disease progression. Normal mammary epithelial cells are heterogeneous and organized in hierarchical fashion, in which the mammary stem cells (MaSC) lie at the apex with regenerative capacity as well as plasticity. Despite the fact that the majority of studies supported the existence of multipotent MaSCs giving rise to both basal and luminal lineages, others proposed lineage restricted unipotent MaSCs. Consistent with the notion, the latest research has suggested that although normal MaSC subsets mainly stay in a quiescent state, they differ in their reconstituting ability, spatial localization, and molecular and epigenetic signatures in response to physiological stimuli within the respective microenvironment during the stages of mammary gland development. In this review, we will focus on current research on the biology of normal mammary stem cells with an emphasis on properties of cellular plasticity, self-renewal and quiescence, as well as the role of the microenvironment in regulating these processes. This will include a discussion of normal breast stem cell heterogeneity, stem cell markers, and lineage tracing studies.
Trabecular architecture in the humeral metaphyses of non‐avian reptiles (Crocodylia, Squamata and Testudines): Lifestyle, allometry and phylogeny

The lifestyle of extinct tetrapods is often difficult to assess when clear morphological adaptations such as swimming paddles are absent. According to the hypothesis of bone functional adaptation, the architecture of trabecular bone adapts sensitively to physiological loadings. Previous studies have already shown a clear relation between trabecular architecture and locomotor behavior, mainly in mammals and birds. However, a link between trabecular architecture and lifestyle has rarely been examined. Here, we analyzed trabecular architecture of different clades of reptiles characterized by a wide range of lifestyles (aquatic, amphibious, generalist terrestrial, fossorial, and climbing). Humeri of squamates, turtles, and crocodylians have been scanned with microcomputed tomography. We selected spherical volumes of interest centered in the proximal metaphyses and measured trabecular spacing, thickness and number, degree of anisotropy, average branch length, bone volume fraction, bone surface density, and connectivity density. Only bone volume fraction showed a significant phylogenetic signal and its significant difference between squamates and other reptiles could be linked to their physiologies. We found negative allometric relationships for trabecular thickness and spacing, positive allometries for connectivity density and trabecular number and no dependence with size for degree of anisotropy and bone volume fraction. The different lifestyles are well separated in the morphological space using linear discriminant analyses, but a cross‐validation procedure indicated a limited predictive ability of the model. The trabecular bone anisotropy has shown a gradient in turtles and in squamates: higher values in amphibious than terrestrial taxa. These allometric scalings, previously emphasized in mammals and birds, seem to be valid for all amniotes. Discriminant analysis has offered, to some extent, a distinction of lifestyles, which however remains difficult to strictly discriminate. Trabecular architecture seems to be a promising tool to infer lifestyle of extinct tetrapods, especially those involved in the terrestrialization.
Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib.

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib improves patient outcomes in chronic lymphocytic leukemia (CLL); however, some patients experience adverse events (AEs) leading to discontinuation. Acalabrutinib is a potent, covalent BTK inhibitor with greater selectivity than ibrutinib. We evaluated the safety and efficacy of 100 mg of acalabrutinib twice daily or 200 mg once daily in patients with CLL who discontinued ibrutinib because of intolerance as determined by the investigators. Among 33 treated patients (61% men; median age, 64 years; range, 50-82 years), median duration of prior ibrutinib treatment was 11.6 months (range, 1-62 months); median time from ibrutinib discontinuation to acalabrutinib start was 47 days (range, 3-331 days). After a median of 19.0 months (range, 0.2-30.6 months), 23 patients remained on acalabrutinib; 10 had discontinued (progressive disease, n = 4; AEs, n = 3). No acalabrutinib dose reductions occurred. During acalabrutinib treatment, the most frequent AEs included diarrhea (58%), headache (39%), and cough (33%). Grade 3/4 AEs occurred in 58%, most commonly neutropenia (12%) and thrombocytopenia (9%). Of 61 ibrutinib-related AEs associated with intolerance, 72% did not recur and 13% recurred at a lower grade with acalabrutinib. Overall response rate was 76%, including 1 complete and 19 partial responses and 5 partial responses with lymphocytosis. Among 25 responders, median duration of response was not reached. Median progression-free survival (PFS) was not reached; 1-year PFS was 83.4% (95% confidence interval, 64.5%-92.7%). Acalabrutinib was well tolerated with a high response rate in patients who were previously intolerant to ibrutinib. This trial was registered at www.clinicaltrials. gov as #NCT02029443.
Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors

Purpose: Here, we report results of the first phase I study of erdafitinib, a potent, oral pan-FGFR inhibitor. Patients and Methods: Patients age ≥18 years with advanced solid tumors for which standard antineoplastic therapy was no longer effective were enrolled (NCT01703481). Parts 2 to 4 employed molecular screening for activating FGFR genomic alterations. In patients with such alterations, two selected doses/schedules identified during part 1 dose-escalation [9 mg once daily and 10 mg intermittently (7 days on/7 days off), as previously published (Tabernero JCO 2015;33:3401-8)] were tested. Results: The study included 187 patients. The most common treatment-related adverse events were hyperphosphatemia (64%), dry mouth (42%), and asthenia (28%), generally grade 1/2 severity. All cases of hyperphosphatemia were grade 1/2 except for 1 grade 3 event. Skin, nail, and eye changes were observed in 43%, 33%, and 28% of patients, respectively (mostly grade 1/2 and reversible after temporary dosing interruption). Urothelial carcinoma and cholangiocarcinoma were most responsive to erdafitinib, with objective response rates (ORR) of 46.2% (12/26) and 27.3% (3/11), respectively, in response-evaluable patients with FGFR mutations or fusions. All patients with urothelial carcinoma and cholangiocarcinoma who responded to erdafitinib carried FGFR mutations or fusions. Median response duration was 5.6 months for urothelial carcinoma and 11.4 months for cholangiocarcinoma. ORRs in other tumor types were <10%. Conclusions: Erdafitinib shows tolerability and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway, at two different dosing schedules and with particularly encouraging responses in urothelial carcinoma and cholangiocarcinoma.
c-Met as a new marker of cellular senescence

Here, we reported for the first time an increased expression of c-Met protein in primary cultures of human dermal and pulmonary fibroblasts of late passages. This suggests that c-Met could serve as an early marker of cellular senescence (CS). The levels of c-Met-related signaling proteins phospho-Akt and Stat3 were also increased in (pre)senescent fibroblasts. Considering the anti-apoptotic activity of Akt and the involvement of Stat3 in mediating the effects of proinflammatory cytokines, the findings of this study indicate that c-Met could contribute through its downstream targets or partners to at least two major phenotypical features of CS – resistance to apoptosis and senescence-associated secretory phenotype.
Position‐specific residue preference features around the ends of helices and strands and a novel strategy for the prediction of secondary structures

It has been many years since position‐specific residue preference around the ends of a helix was revealed. However, all the existing secondary structure prediction methods did not exploit this preference feature, resulting in low accuracy in predicting the ends of secondary structures. In this study, we collected a relatively large data set consisting of 1860 high‐resolution, non‐homology proteins from the PDB, and further analyzed the residue distributions around the ends of regular secondary structures. It was found that there exist position‐specific residue preferences (PSRP) around the ends of not only helices but also strands. Based on the unique features, we proposed a novel strategy and developed a tool named E‐SSpred that treats the secondary structure as a whole and builds models to predict entire secondary structure segments directly by integrating relevant features. In E‐SSpred, the support vector machine (SVM) method is adopted to model and predict the ends of helices and strands according to the unique residue distributions around them. A simple linear discriminate analysis method is applied to model and predict entire secondary structure segments by integrating end‐prediction results, tri‐peptide composition, and length distribution features of secondary structures, as well as the prediction results of the most famous program PSIPRED. The results of fivefold cross‐validation on a widely used data set demonstrate that the accuracy of E‐SSpred in predicting ends of secondary structures is about 10% higher than PSIPRED, and the overall prediction accuracy (Q3 value) of E‐SSpred (82.2%) is also better than PSIPRED (80.3%). The E‐SSpred web server is available at http://bioinfo.hust. edu.cn/bio/tools/E‐SSpred/index.html.
Recovery of Human Metapneumovirus Genetic Lineages A and B from Cloned cDNA

ABSTRACT Human metapneumovirus (hMPV) is a newly discovered pathogen associated with respiratory tract illness, primarily in young children, immunocompromised individuals, and the elderly. The genomic sequence of the prototype hMPV isolate NL/1/00 without the terminal leader and trailer sequences has been reported previously. Here we describe the leader and trailer sequences of two hMPV isolates, NL/1/00 and NL/1/99, representing the two main genetic lineages of hMPV. Minigenome constructs in which the green fluorescent protein or chloramphenicol acetyltransferase genes are flanked by the viral genomic ends derived from both hMPV lineages and transcribed using a T7 RNA polymerase promoter-terminator cassette were generated. Cotransfection of minigenome constructs with plasmids expressing the polymerase complex components L, P, N, and M2.1 in 293T or baby hamster kidney cells resulted in expression of the reporter genes. When the minigenome was replaced by a sense or antisense full-length cDNA copy of the NL/1/00 or NL/1/99 viral genomes, recombinant virus was recovered from transfected cells. Viral titers up to 107.2 and 105.7 50% tissue culture infective dose/ml were achieved with the sense and antisense plasmids, respectively. The recombinant viruses replicated with kinetics similar to those of the parental viruses in Vero cells. This reverse genetics system provides an important new tool for applied and fundamental research.
Adverse Childhood Experiences Are Linked to Age of Onset and Reading Recognition in Multiple Sclerosis

Background Adverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood. Objective To investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS). Methods Sixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation. Results Adverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset (r = –0.30, p = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) (r = –0.25, p = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). Conclusion Childhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS.
A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction

Two-dimensional (2D) human skeletal muscle fiber cultures are ill-equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron endplates. Here we describe a three-dimensional (3D) co-culture method whereby human muscle progenitors mixed with human pluripotent stem cell-derived motor neurons self-organize to form functional NMJ connections. Functional connectivity between motor neuron endplates and muscle fibers is confirmed with calcium imaging and electrophysiological recordings. Notably, we only observed epsilon acetylcholine receptor subunit protein upregulation and activity in 3D co-cultures. Further, 3D co-culture treatments with myasthenia gravis patient sera shows the ease of studying human disease with the system. Hence, this work offers a simple method to model and evaluate adult human NMJ de novo development or disease in culture.