Miracle-dz/UniFAR-FTUs huggingface dataset:
Right hemispheric structural connectivity and poststroke language recovery

Poststroke aphasia typically results from brain damage to the left‐lateralized language network. The contribution of the right‐lateralized homologues in aphasia recovery remains equivocal. In this longitudinal observational study, we specifically investigated the role of right hemisphere structural connectome in aphasia recovery. Twenty‐two patients with aphasia after a left hemispheric stroke underwent comprehensive language assessment at the early subacute and chronic stages. A novel structural connectometry approach, using multi‐shell diffusion‐weighted MRI data collected at the early subacute stage, was used to evaluate the relationship between right hemisphere white matter connectome and language production and comprehension abilities at early subacute stage. Moreover, we evaluated the relationship between early subacute right hemisphere white matter connectome and longitudinal change in language production and comprehension abilities. All results were corrected for multiple comparisons. Connectometry analyses revealed negative associations between early subacute stage right hemisphere structural connectivity and language production, both cross‐sectionally and longitudinally (pFDR < .0125). In turn, only positive associations between right hemisphere structural connectivity and language comprehension were observed, both cross‐sectionally and longitudinally (pFDR < .0125). Interhemispheric connectivity was highly associated with comprehension scores. Our results shed light on the discordant interpretations of previous findings, by providing evidence that while some right hemisphere white matter pathways may make a maladaptive contribution to the recovery of language, other pathways support the recovery of language, especially comprehension abilities.
Vascular stability of brain arteriovenous malformations after partial embolization

Abstract Introduction Brain arteriovenous malformation (bAVM) might have a higher risk of rupture after partial embolization, and previous studies have shown that some metrics of vascular stability are related to bAVM rupture risk. Objective To analyze vascular stability of bAVM in patients after partial embolization. Methods Twenty‐four patients who underwent partial embolization were classified into the short‐term, medium‐term, and long‐term groups, according to the time interval between partial embolization and surgery. The control group consisted of 9 bAVM patients who underwent surgery alone. Hemodynamic changes after partial embolization were measured by angiogram. The inflammatory infiltrates and cell–cell junctions were evaluated by MMP‐9 and VE‐cadherin. At the protein level, the proliferative and apoptotic events of bAVMs were analyzed by immunohistochemical staining of VEGFA, eNOS, and caspase‐3. Finally, neovascularity and apoptotic cells were assessed by CD31 staining and TUNEL staining. Results Immediately after partial embolization, the blood flow velocity of most bAVMs increased. The quantity of MMP‐9 in the medium‐term group was the highest, and VE‐cadherin in the medium‐term group was the lowest. The expression levels of VEGFA, eNOS, and neovascularity were highest in the medium‐term group. Similarly, the expression level of caspase‐3 and the number of apoptotic cells were highest in the medium‐term group. Conclusion The biomarkers for bAVM vascular stability were most abnormal between 1 and 28 days after partial embolization.
The production of Spanish–English code-switching

It is generally assumed that in code-switching (CS) switches between two languages are categorical, however, recent research suggests that the phonologies involved in CS are merged and bilinguals must actively suppress one language when encoding in the other. Thus, it was hypothesized that CS does not take place abruptly but that cues before the point of language change are also present. This hypothesis is tested with a corpus of Spanish-English CS examining word-initial voiceless stop VOT and the vowel in the discourse marker “like. ” English VOTs at CS boundaries were shorter, or more “Spanish-like,” than in monolingual utterances. Preliminary results suggest Spanish VOTs at CS boundaries were shorter than in monolingual utterances, thus even more Spanish-like than monolingual Spanish utterances. The vowel of “like” in English utterances was more monophthongal and had a lower final F2 as compared to “like” in Spanish utterances. At CS boundaries, “like” began similarly to the language preceding the token.
Building reflective spaces for junior doctors to promote ethical, legal and professional learning relating to clinical practice

Concerns have been raised surrounding the training of Foundation Doctors on the ethical, legal and professionalism (ELP) aspects of clinical practice, leading to some to claim a degree of educational neglect. Foundation Doctors are junior doctors in the United Kingdom within the first 2 years of their medical career since graduating from medical school.
Systematic Exploration of SARS-CoV-2 Adaptation to Vero E6, Vero E6/TMPRSS2, and Calu-3 Cells

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, and scientists around the world are currently studying the virus intensively in order to fight against the on-going pandemic of the virus. To do so, SARS-CoV-2 is typically grown in the lab to generate viral stocks for various kinds of experimental investigations. However, accumulating evidence suggests that such viruses often undergo cell culture adaptation. Here, we systematically explored cell culture adaptation of two SARS-CoV-2 variants, namely the B.1. 36.16 variant and the AY.30 variant, a sub lineage of the B.1. 617.2 (Delta) variant, propagated in three different cell lines, including Vero E6, Vero E6/TMPRSS2, and Calu-3 cells. Our analyses detected numerous potential cell culture adaptation changes scattering across the entire virus genome, many of which could be found in naturally circulating isolates. Notable ones included mutations around the spike glycoprotein's multibasic cleavage site, and the Omicron-defining H655Y mutation on the spike glycoprotein, as well as mutations in the nucleocapsid protein's linker region, all of which were found to be Vero E6-specific. Our analyses also identified deletion mutations on the non-structural protein 1 and membrane glycoprotein as potential Calu-3-specific adaptation changes. S848C mutation on the non-structural protein 3, located to the protein's papain-like protease domain, was also identified as a potential adaptation change, found in viruses propagated in all three cell lines. Our results highlight SARS-CoV-2 high adaptability, emphasize the need to deep-sequence cultured viral samples when used in intricate and sensitive biological experiments, and illustrate the power of experimental evolutionary study in shedding lights on the virus evolutionary landscape.
RND Pump-Mediated Efflux of Amotosalen, a Compound Used in Pathogen Inactivation Technology to Enhance Safety of Blood Transfusion Products, May Compromise Its Gram-Negative Anti-Bacterial Activity

Pathogen inactivation is a strategy to enhance the safety of transfused blood products. We identify the compound, amotosalen, widely used for pathogen inactivation, as a bacterial multidrug efflux substrate. ABSTRACT Pathogen inactivation is a strategy to improve the safety of transfusion products. The only pathogen reduction technology for blood products currently approved in the US utilizes a psoralen compound, called amotosalen, in combination with UVA light to inactivate bacteria, viruses, and protozoa. Psoralens have structural similarity to bacterial multidrug efflux pump substrates. As these efflux pumps are often overexpressed in multidrug-resistant pathogens, we tested whether contemporary drug-resistant pathogens might show resistance to amotosalen and other psoralens based on multidrug efflux mechanisms through genetic, biophysical, and molecular modeling analysis. The main efflux systems in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa are tripartite resistance-nodulation-cell division (RND) systems, which span the inner and outer membranes of Gram-negative pathogens, and expel antibiotics from the bacterial cytoplasm into the extracellular space. We provide evidence that amotosalen is an efflux substrate for the E. coli AcrAB, Acinetobacter baumannii AdeABC, and P. aeruginosa MexXY RND efflux pumps. Furthermore, we show that the MICs for contemporary Gram-negative bacterial isolates for these species and others in vitro approached and exceeded the concentration of amotosalen used in the approved platelet and plasma inactivation procedures. These findings suggest that otherwise safe and effective inactivation methods should be further studied to identify possible gaps in their ability to inactivate contemporary, multidrug-resistant bacterial pathogens. IMPORTANCE Pathogen inactivation is a strategy to enhance the safety of transfused blood products. We identify the compound, amotosalen, widely used for pathogen inactivation, as a bacterial multidrug efflux substrate. Specifically, experiments suggest that amotosalen is pumped out of bacteria by major efflux pumps in E. coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. Such efflux pumps are often overexpressed in multidrug-resistant pathogens. Importantly, the MICs for contemporary multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Burkholderia spp. , and Stenotrophomonas maltophilia isolates approached or exceeded the amotosalen concentration used in approved platelet and plasma inactivation procedures, potentially as a result of efflux pump activity. Although there are important differences in methodology between our experiments and blood product pathogen inactivation, these findings suggest that otherwise safe and effective inactivation methods should be further studied to identify possible gaps in their ability to inactivate contemporary, multidrug-resistant bacterial pathogens.
Serum Progesterone is Negatively Associated with Hypertension and Blood Pressure Indicators Among Men and Postmenopausal Women

Abstract Sex hormones have been shown to be negatively associated with hypertension, but the relationship between serum progesterone levels and hypertension has not been adequately studied. Therefore, we aimed to evaluate the association between progesterone and hypertension among Chinese rural adults. A total of 6222 participants were recruited, which included 2577 men and 3645 women. The concentration of serum progesterone was detected by liquid chromatography-mass spectrometer system (LC-MS/MS). Logistic regression and linear regression were used to assess the associations between progesterone levels and hypertension and blood pressure related indicators, respectively. Constrained splines were used to fit the dose-response relationships of progesterone with hypertension and blood pressure related indicators. Moreover, the interactive effects of several lifestyle factors and progesterone were identified by a generalized linear model. After fully adjusting the variables, progesterone levels were inversely associated with hypertension in men [odds ratio (OR): 0.851, 95% confidence interval (CI): 0.752, 0.964]. Among men, a 2.738 ng/ml increase in progesterone was associated with a 0.557 mmHg decrease in diastolic blood pressure (DBP) (95% CI: –1.007, –0.107) and a 0.541 mmHg decrease in mean arterial pressure (MAP) (95% CI: –1.049, –0.034), respectively. Similar results were observed in postmenopausal women. Interactive effect analysis showed that only a significant interaction was observed between progesterone and educational attainment on hypertension in premenopausal women (p=0.024). Elevated levels of serum progesterone were associated with hypertension in men. Except for premenopausal women, a negative association of progesterone with blood pressure related indicators was observed.
Resource utilization and costs for robotic-assisted and manual total knee arthroplasty – a premier healthcare database study

ABSTRACT Introduction The impact of robotic-assisted total knee arthroplasty (rTKA) vs. traditional, manual TKA (mTKA) on hospital costs is not well documented and is analyzed herein. Research Design and Methods Patients in the Premier billing Healthcare Database undergoing elective rTKA or mTKA (“index’) in the in- or outpatient setting for knee osteoarthritis between Oct 1st, 2015, to September 30th, 2021, were identified. Variables included patient demographics and comorbidities and hospital characteristics. Matched rTKA vs. mTKA cohorts were created using direct (on provider characteristics, age, gender, race and Elixhauser index) and propensity score matching (fixation type, comorbidities). Index and 90-day inflation-adjusted costs and healthcare utilization (HCU) were analyzed for both cohorts, using generalized linear models. Results 16,714 rTKA patients were matched to 51,199 mTKA patients. Average 90-day hospital cost reached $17,932 and were equivalent for both cohorts (rTKA vs. mTKA: $132 (95% confidence interval; -$19 to $284). There was a 2.7% (95%CI: 2.2%-3.3%) increase in home or home health discharge, and a 0.4% (95%CI: 0%-0.8%) decrease in 90-day hospital knee related re-visit in the rTKA vs. mTKA group. Conclusions Cost-neutrality of rTKA vs. mTKA was observed, with a potential for lowered immediate post-operative HCU in the rTKA vs. mTKA cohorts.
Prevalence of Pathogenic Germline Mutations in 13 Hereditary Cancer-Related Genes in Breast Cancer Patients in Narathiwat Province, Thailand

Background: BRCA1 and BRCA2 genes are known to increase breast cancer’s lifetime risk. Early identification of women with this inherited risk can potentially reduce the risk of breast and/or ovarian cancer and, together with early screening, decrease the mortality rate. Objective: This study explored the frequency and distribution of genetic variants in consecutive cases of breast cancer in Narathiwat province, one of the three provinces in the southernmost Thai border. Material & Method: A series of 64 consecutive breast cancer patients who underwent treatment in two general hospitals in the province during the period from the year 2021 to 2022. Genotyping studies were performed using a whole exome sequencing platform. Moderate to high penetrance variants recommended by the National Comprehensive Cancer Network (NCCN) guidelines 2022 (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53) were annotated and filtered for pathogenic, likely pathogenic, or high-impact variants. Results: Pathogenic germline variants were found in 8/64 cases (12.5%), namely BRCA1 in 3 (4.7%), BRCA2 in 4 (6.3%), ATM in 1 (1.6%), and PALB2 in 1 (1.6%). One patient had two concomitant germline mutations in BRCA2 and ATM. Conclusion: This is the first study on the frequency of germline mutations in BRCA1/2 and other breast cancer-predisposing genes in the southernmost provinces of Thailand. At least one pathogenic germline mutation was identified in 12.5% of the study patients, which suggests that genetic testing in this population has a high potential to provide benefits.
Mineralogical characterization of biosilicas versus geological analogs

Non‐crystalline silica mineraloids are essential to life on Earth as they provide architectural structure to dominant primary producers, such as plants and phytoplankton, as well as to protists and sponges. Due to the difficulty in characterizing and quantifying the structure of highly disordered X‐ray amorphous silica, relatively little has been done to understand the mineralogy of biogenic silica and how this may impact the material properties of biogenic silica, such as hardness and strength, or how biosilica might be identified and differentiated from its inorganic geological counterparts. Typically, geologically formed opal‐A and hyalite opal‐AN are regarded as analogs to biogenic silica, however, some spectroscopic and imaging studies suggest that this might not be a reasonable assumption. In this study, we use a variety of techniques (X‐ray diffraction, Raman spectroscopy, and scanning electron microscopy) to compare differences in structural disorder and bonding environments of geologically formed hydrous silicas (Opal‐A, hyalite, geyserite) and silica glass versus biogenic silicas from an array of organisms. Our results indicate differences in the levels of structural disorder and the Raman‐observed bonding environments of the SiO2 network modes (D1 mode) and the Q‐species modes (~1015 cm−1) between varieties of biogenic silicas and geologically formed silicas, which aligns with previous studies that suggest fundamental differences between biogenic and geologically formed silica. Biosilicas also differ structurally from one another by species of organism. Our mineralogical approach to characterizing biosilicas and differentiating them from other silicas may be expanded to future diagenesis studies, and potentially applied to astrobiology studies of Earth and other planets.
Interannual atmosphere-ocean variations in the tropical western North Pacific relevant to the Asian summer monsoon-ENSO coupling

Using an ocean general circulation model (OGCM) forced by daily mean wind stresses and heat fluxes derived from the bulk formulation with the NCEP/NCAR reanalysis of 1973-1995, we examined interannual atmosphere-ocean variations in the tropical western North Pacific related to the Asian summer monsoon-ENSO coupling. The OGCM simulation was successful in reproducing the east-west gradient of summertime SST anomalies between the South China Sea and the tropical western Pacific east of the Philippines that is linked with anomalous tropical convection in that vicinity. A heat budget analysis shows that a longitudinal asymmetry of surface latent heat flux anomalies is crucially responsible for the reinforcement and persistence of the east-west gradient of SST anomalies between the two regions. It is also found that the transition from premonsoon regime to monsoon regime in the tropical Indian Ocean affects the interannual atmosphere-ocean variations in the tropical western North Pacific during the period from the late 1970s to the early 1990s. In the spring before strong Asian summer monsoon, an equatorially asymmetric air-sea coupled mode tends to appear in the tropical Indian Ocean. Simultaneously with the beginning of the strong monsoon regime, the northern Indian Ocean and South China Sea are covered by cool SST anomalies due to enhanced wind speed and evaporation, whereas warm anomalies relevant to a cold episode of ENSO are still maintained in the warm pool region east of the Philippines. The latitudinally asymmetric anomalies of tropical convection and SST become dissipated and convection over the warm pool region of the western North Pacific becomes localized and enhanced with the establishment of east-west gradient of SST anomalies. Due to enhanced convective heating, equatorially asymmetric atmospheric Rossby waves are excited to the west of anomalous convection, which induce low-level westerly anomalies. This dynamic process further facilitates the localization of intense convection through the change in surface latent heat flux and SST. While such a positive atmosphere-ocean feedback system persists in boreal summer, the Pacific and Japan (PJ) teleconnection pattern in response to enhanced convection prevails and brings about unusually hot summers in recent years especially in the vicinity of Japan.
Fine regularity of Lévy processes and linear (multi)fractional stable motion

In this work, we investigate the fine regularity of Levy processes using the 2-microlocal formalism. This framework allows us to refine the multifractal spectrum determined by Jaffard and, in addition, study the oscillating singularities of Levy processes. The fractal structure of the latter is proved to be more complex than the classic multifractal spectrum and is determined in the case of alpha-stable processes. As a consequence of these fine results and the properties of the 2-microlocal frontier, we are also able to completely characterise the multifractal nature of the linear fractional stable motion (extension of fractional Brownian motion to α-stable measures) in the case of continuous and unbounded sample paths as well. The regularity of its multifractional extension is also presented, indirectly providing an example of a stochastic process with a non-homogeneous and random multifractal spectrum.
A meta‐analysis of the neural substrates of monetary reward anticipation and outcome in alcohol use disorder

The capacity to anticipate and detect rewarding outcomes is fundamental for the development of adaptive decision‐making and goal‐oriented behavior. Delineating the neural correlates of different stages of reward processing is imperative for understanding the neurobiological mechanism underlying alcohol use disorder (AUD). To examine the neural correlates of monetary anticipation and outcome in AUD patients, we performed two separate voxel‐wise meta‐analyses of functional neuroimaging studies, including 12 studies investigating reward anticipation and 7 studies investigating reward outcome using the monetary incentive delay task. During the anticipation stage, AUD patients displayed decreased activation in response to monetary cues in mesocortical‐limbic circuits and sensory areas, including the ventral striatum (VS), insula, hippocampus, inferior occipital gyrus, supramarginal gyrus, lingual gyrus and fusiform gyrus. During the outcome stage, AUD patients exhibited reduced activation in the dorsal striatum, VS and insula, and increased activation in the orbital frontal cortex and medial temporal area. Our findings suggest that different activation patterns are associated with nondrug rewards during different reward processing stages, potentially reflecting a changed sensitivity to monetary reward in AUD.
Excitatory brain stimulation over the left dorsolateral prefrontal cortex enhances voluntary distraction in depressed patients

Abstract Background While implicit distraction could ameliorate negative feelings in patients with major depressive disorders (MDD), it remains unclear whether patients could benefit from explicit, voluntary distraction. Meanwhile, though the dorsolateral prefrontal cortex (DLPFC) is established as a crucial brain region involved in attentional control, the causal relationship between the DLPFC and voluntary distraction is unexplored in patients. Methods Combing explicit distraction and transcranial magnetic stimulation (TMS), this study investigated whether TMS-activated DLPFC facilitates voluntary distraction in MDD patients. Eighty patients diagnosed with current MDD underwent either active (n = 40) or sham (n = 40) TMS sessions, followed by receiving negative social feedback from other patients, during which they were requied to use distraction strategy to down-regulate their painful feelings. Electroencephalogram was recorded during the task. Results Both the subjective emotional rating and the amplitude of late positive potential showed that depressed patients successfully down-regulate their negative emotions via voluntary distraction, and the TMS-activated left DLPFC produced a larger benefit of emotion regulation compared to the sham TMS group. Results also revealed that while emotion regulation effect was negatively associated with depressive symptoms in the sham TMS group, this correlation was largely diminished when patients' left DLPFC was activated by TMS during the voluntary distraction. Conclusions These findings demonstrated that distraction is valuable for emotion regulation in MDD patients and they could be beneficial in voluntary distraction by activating their left DLPFC using neural modulation techniques. This study has valuable implications for clinical treatement of emotional dysregulation in MDD patients.