Miracle-dz/UniFAR-FTUs huggingface dataset:
Serotonin transporter in the temporal lobe, hippocampus and amygdala in SUDEP

Several lines of evidence link deficient serotonin function and SUDEP. Chronic treatment with serotonin reuptake inhibitors (SRIs) reduces ictal central apnoea, a risk factor for SUDEP. Reduced medullary serotonergic neurones, modulators of respiration in response to hypercapnia, were reported in a SUDEP post‐mortem series. The amygdala and hippocampus have high serotonergic innervation and are functionally implicated in seizure‐related respiratory dysregulation. We explored serotonergic networks in mesial temporal lobe structures in a surgical and post‐mortem epilepsy series in relation to SUDEP risk. We stratified 75 temporal lobe epilepsy patients with hippocampal sclerosis (TLE/HS) into high (N = 16), medium (N = 11) and low risk (N = 48) groups for SUDEP based on generalised seizure frequency. We also included the amygdala in 35 post‐mortem cases, including SUDEP (N = 17), epilepsy controls (N = 10) and non‐epilepsy controls (N = 8). The immunohistochemistry labelling index (LI) and axonal length (AL) of serotonin transporter (SERT)‐positive axons were quantified in 13 regions of interest with image analysis. SERT LI was highest in amygdala and subiculum regions. In the surgical series, higher SERT LI was observed in high risk than low risk cases in the dentate gyrus, CA1 and subiculum (p < 0.05). In the post‐mortem cases higher SERT LI and AL was observed in the basal and accessory basal nuclei of the amygdala and peri‐amygdala cortex in SUDEP compared to epilepsy controls (p < 0.05). Patients on SRI showed higher SERT in the dentate gyrus (p < 0.005) and CA4 (p < 0.05) but there was no difference in patients with or without a psychiatric history. Higher SERT in hippocampal subfields in TLE/HS cases with SUDEP risk factors and higher amygdala SERT in post‐mortem SUDEP cases than epilepsy controls supports a role for altered serotonergic networks involving limbic regions in SUDEP. This may be of functional relevance through reduced 5‐HT availability.
Sharing, reuse, and storage of biosamples among biomedical researchers in Jordan: Practice and concerns

Background Sharing and reuse biosamples can facilitate biomedical research. Little is known about researchers’ perception and practice about sharing, reusing, and storing biosamples in Jordan. Therefore, the current study aimed to evaluate the practices of biomedical researchers in Jordan regarding biosamples management. Methods The study was cross-sectional and involved biomedical researchers from different parts of Jordan. A questionnaire was designed to achieve the aim of this study. The questionnaire was web-based and distributed via e-mails using Google forms. Results Opinions of Jordanian biomedical researchers from different academic ranks and institutional backgrounds were measured and recorded anonymously. The majority of the sample was males (57.9%), from public universities (64.3%), and (64.6%) were from health-related fields. About 82.9% of participants stored biosamples using codes, whereas the rest used the subject’s name. Sharing of biosamples was commonly practiced by 61.7% of Jordanian researchers locally, while 47.2% of the Jordanian researchers shared biosamples overseas. The reuse of biosamples in other projects was reported to be 55.4%. The majority explained the possibility of reusing and sharing biosamples in the consent form (range: 53–58%). Sharing and reusing biosamples were associated with gender, the number of publications in peer-reviewed international journals, and academic rank (P<0.05). Conclusion Sharing and reusing biosamples are common among Jordanian biomedical researchers. Therefore, ethically grounded biosamples sharing and reuse standards are essential for protecting human subjects’ rights and privacy in Jordan.
Lethal synergy between SARS-CoV-2 and Streptococcus pneumoniae in hACE2 mice and protective efficacy of vaccination.

Secondary infections are frequent complications of viral respiratory infections but the potential consequence of SARS-CoV-2 co-infection with common pulmonary pathogens is poorly understood. We report that co-infection of human ACE2 transgenic mice with sublethal doses of SARS-CoV-2 and Streptococcus pneumoniae results in synergistic lung inflammation and lethality. Mortality was observed regardless of whether SARS-CoV-2 challenge occurred before or after establishment of sublethal pneumococcal infection. Increased bacterial levels following co-infection were associated with alveolar macrophage depletion and treatment with murine GM-CSF reduced lung bacteria numbers and pathology, and partially protected from death. However, therapeutic targeting of interferons, an approach that is effective against influenza co-infections, failed to increase survival. Combined vaccination against both SARS-CoV-2 and pneumococci resulted in 100% protection against subsequent co-infection. The results indicate that when seasonal respiratory infections return to pre-pandemic levels, they could lead to an increased incidence of lethal COVID-19 superinfections, especially among the unvaccinated population.
Lysophosphatidylcholine induces azurophil granule translocation via Rho/Rho kinase/F-actin polymerization in human neutrophils

Translocation of azurophil granules is pivotal for bactericidal activity of neutrophils, the first-line defense cells against pathogens. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances bactericidal activity of human neutrophils via increasing translocation of azurophil granules. However, the precise mechanism of LPC-induced azurophil granule translocation was not fully understood. Treatment of neutrophil with LPC significantly increased CD63 (an azurophil granule marker) surface expression. Interestingly, cytochalasin B, an inhibitor of action polymerization, blocked LPC-induced CD63 surface expression. LPC increased F-actin polymerization. LPC-induced CD63 surface expression was inhibited by both a Rho specific inhibitor, Tat-C3 exoenzyme, and a Rho kinase (ROCK) inhibitor, Y27632 which also inhibited LPC-induced F-actin polymerization. LPC induced Rho-GTP activation. NSC23766, a Rac inhibitor, however, did not affect LPC-induced CD63 surface expression. Theses results suggest a novel regulatory mechanism for azurophil granule translocation where LPC induces translocation of azurophil granules via Rho/ROCK/F-actin polymerization pathway.
What would reduce caesarean section rates?—Views from pregnant women and clinicians in Ireland

Background Caesarean section rates continue to rise in most parts of the world. While CS is a lifesaving procedure there is evidence that, beyond a certain threshold, CS rates may contribute to increased maternal and perinatal morbidity. This study aimed to elicit the views of pregnant women’s and clinicians’ on how CS rates might be reduced. Methods Pregnant women and their partners, and clinicians working with pregnant women in a maternity hospital in the Republic of Ireland of Ireland, were invited to participate in focus groups. Eligibility criteria included all women attending antenatal classes and clinicians working with pregnant women. A convenience sample was used and interviews were audio recorded, transcribed, and analysed using thematic analysis. Results Four focus group interviews were conducted with 30 clinicians and 15 pregnant women and two partners participated in three focus groups. A further two women were interviewed individually. Participants expressed a view that rising CS rates were impacted by a societal perception that CS had become a ‘normal mode of birth’. Suggestions for reducing CS rates were offered by clinicians and pregnant women and their partners. Conclusions Clinicians and pregnant women consider that CS rates can be reduced if a shared philosophy supporting normal birth is prioritised alongside adequate resourcing. Women and their partners also believe that enhanced communication with clinicians is central to reducing CS rates.
Impaired Stretch-Shortening Cycle Function Persists Despite Improvements in Reactive Strength After Anterior Cruciate Ligament Reconstruction

Abstract Read, PJ, Pedley, JS, Eirug, I, Sideris, V, and Oliver, JL. Impaired stretch-shortening cycle function persists despite improvements in reactive strength followingafter anterior cruciate ligament reconstruction. J Strength Cond Res 36(5): 1238–1244, 2022—Reactive strength index (RSI) during a single-leg drop jump (SLDJ) has been indicated to determine return-to-sport readiness after anterior cruciate ligament (ACL) reconstruction, but only cross-sectional studies are available. Ground reaction force data and characterization of stretch-shortening cycle (SSC) function also remain sparse. Single-leg drop jump performance, ground reaction force, and SSC function were examined in soccer players with ACL reconstruction (n = 26) and matched controls (n = 25). Injured players were tested at 2 time points (32 and 42 weeks postsurgery). Stretch-shortening cycle function was classified as good (no impact peak and spring like), moderate (impact peak but still spring like or no impact peak and not spring like), or poor (impact peak and not spring like). The involved limb displayed lower-jump height, poorer RSI, less spring-like behavior, earlier peak landing force, and a greater ratio of landing peak to take-off peak force compared with the uninvolved limb and controls at the initial assessment (p < 0.001). Proportionally, more involved limbs were categorized as poor or moderate at the initial assessment (69.2%) and follow-up (50%) in comparison with the control limbs (14%). The reactive strength index was the only variable to change significantly between the initial assessment and follow-up on the involved limb (p < 0.05). No changes in the proportion of ACL reconstructed individuals categorized as poor or moderate SSC function at the follow-up assessment were observed. Residual deficits are present in SLDJ performance, SSC function, and ground reaction force characteristics after ACL reconstruction. The reactive strength index should not be the sole metric, as observed increases did not correspond with changes in SSC function.
Health Literacy, Cognitive Impairment, and Diabetes Knowledge Among Incarcerated Persons Transitioning to the Community

ABSTRACT Purpose The purpose of this study was to evaluate the relationships of health literacy (HL; Short Test of Functional Health Literacy), cognitive impairment (CI), and diabetes knowledge (DK) among incarcerated persons transitioning to the community. Methods Using preintervention data from a quasi-experimental nonequivalent control group study evaluating the feasibility of a six-session literacy-tailored Diabetes Survival Skills intervention for incarcerated men transitioning to the community, we conducted correlational analyses among the Short Test of Functional Health Literacy, Montreal Cognitive Assessment, and Spoken Knowledge in Low Literacy in Diabetes Scale using the SPSS PROCESS macro and bias-corrected bootstrapping to test the meditational hypothesis: HL mediates the relationship between CI and DK. Results Participants (N = 73) were incarcerated for 1–30 years with a mean age of 47 (9.9) years, 40% Black, 19% White, and 30% Hispanic, with 78% having high school/GED or less education. Most (70%) screened positive for CI and had low DK, and 20% had marginal or inadequate HL. HL, CI, and DK were positively associated with each other. Controlling for race, age, and group (control/experimental), cognitive function had a significant direct effect on HL (b = 0.866, p = 0.0003) but not on DK (b = 0.119, p = 0.076). Results indicated a significant indirect effect of cognitive functioning on DK via HL, 95% confidence interval [0.300, 0.1882]. Conclusion Intervention approaches aimed at increasing HL or tailored to low HL in the presence of CI may be effective in increasing DK in this population. Implications Given the low risk to high benefit of implementing literacy-tailored approaches to persons in prison and the population demographics from studies supporting a high degree of CI, nurses should consider implementing literacy-tailored approaches and screening for CI before participation in all educational programs.
DNA barcodes reveal striking arthropod diversity and unveil seasonal patterns of variation in the southern Atlantic Forest

The Atlantic Forest harbors 7% of global biodiversity and possesses high levels of endemism, but many of its component taxa remain unstudied. Due to the importance of tropical forests and the urgency to protect them, there is a compelling need to address this knowledge gap. To provide more information on its arthropod fauna, a Malaise trap was deployed for 12 months in a semi-degraded area of the southern Upper Paraná ecoregion of the Atlantic Forest. All specimens were DNA barcoded and the Barcode Index Number (BIN) system was employed to assign each specimen to a species proxy. DNA barcodes were obtained from 75,500 arthropods that included representatives of 8,651 BINs. Nearly 81% of these BINs were first records, highlighting the high rates of endemism and lack of study of arthropods from the Atlantic Forest. Diptera was the most abundant order, followed by Hemiptera, Lepidoptera and Hymenoptera. Diptera was also the most species-rich order, followed by Hymenoptera, Lepidoptera, and Coleoptera, a result consistent with studies in other biogeographic regions. Insects were most abundant in winter and most diverse in autumn and winter. This pattern, however, was caused mainly by the dynamics of dipteran diversity as other orders differed in their seasonal variation. The BIN composition of the insect community varied sharply through the year and also differed between the two consecutive summers included in the sampling period. The study of the 38 commonest BINs showed that seasonal patterns of abundance were not order-specific. Temperature had the strongest impact on seasonal abundance variation. Our results highlight the striking and understudied arthropod diversity of the highly fragmented Atlantic Forest, the predominance of dipterans, and the fact that abundance and richness in this insect community peak in the coolest months. Standardized studies like this generate fast and reliable biodiversity inventories and unveil ecological patterns, thus providing valuable information for conservation programs.
Efficacy of liquid biopsy for disease monitoring and early prediction of tumor progression in EGFR mutation-positive non-small cell lung cancer

15–40% of non-small cell lung cancer (NSCLC) patients harbor epidermal growth factor receptor (EGFR)-sensitizing mutations. Tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in this population, yet all patients will ultimately progress. Liquid biopsy can reliably identify somatic tumor-associated EGFR mutations in plasma. This study aimed to assess the feasibility and value of the quantitative assessment of EGFR driver mutations in plasma in EGFR-mutated NSCLC patients treated with EGFR-TKIs as a tool to evaluate therapeutic response to TKIs and monitor for disease progression. The study included 136 patients with tissue biopsy-confirmed EGFR-sensitizing, mutation-positive lung adenocarcinoma with plasma collected prior to TKI treatment and at least two post-initiation TKI treatment/follow-up blood samples. Plasma samples were tested with the cobas® EGFR Mutation Test v2 (cobas EGFR Test), and semi-quantitative index (SQI) values for each identified mutation were reported by the assay software. The most common baseline EGFR mutations detected in tissue were L858R (53.7%) and exon 19 deletion (39.7%). Plasma cell-free DNA analysis detected EGFR mutations in 74% of the baseline samples. Objective response rate by RECIST 1.1 was achieved in 72% of patients, while 93% had a molecular response (defined as disappearance of the EGFR mutation from plasma). 83% of patients had molecular progression (MP; 1.5X SQI increase or new T790M mutation), and 82% who had a clinical response had clinical progression. On average, MP occurred 42 days prior to clinical progression. Patients who progressed while on first-line TKI showed MP of the original EGFR-sensitizing mutations prior to the emergence of a T790M mutation, which was detected in 27% of the EGFR plasma-positive patients. Longitudinal monitoring of EGFR mutational load in plasma is feasible and can predict both response and clinical progression in EGFR-mutated NSCLC patients treated with EGFR-TKIs, as well as detect treatment-emergent EGFR mutations.
Natural Variation Meets Synthetic Biology: Promiscuous Trichome Expressed Acyltransferases from Nicotiana acuminata

Acylsugars are defensive, trichome-synthesized sugar esters produced in plants across the Solanaceae (nightshade) family. Although assembled from simple metabolites and synthesized by a relatively short core biosynthetic pathway, tremendous within- and across-species acylsugar structural variation is documented across the family. To advance our understanding of the diversity and the synthesis of acylsugars within the Nicotiana genus, trichome extracts were profiled across the genus coupled with transcriptomics-guided enzyme discovery and in vivo and in vitro analysis. Differences in the types of sugar cores, numbers of acylations, and acyl chain structures contributed to over 300 unique annotated acylsugars throughout Nicotiana. Placement of acyl chain length into a phylogenetic context revealed that an unsaturated acyl chain type was detected in a few closely-related species. A comparative transcriptomics approach identified trichome-enriched Nicotiana acuminata acylsugar biosynthetic candidate enzymes. > 25 acylsugar variants could be produced in a single enzyme assay with four acylsugar acyltransferases (NacASAT1-4) together with structurally diverse acyl-CoAs and sucrose. Liquid chromatography coupled with mass spectrometry screening of in vitro products revealed the ability of these enzymes to make acylsugars not present in Nicotiana plant extracts. In vitro acylsugar production also provided insights into acyltransferase acyl donor promiscuity and acyl acceptor specificity as well as regiospecificity of some ASATs. This study suggests that promiscuous Nicotiana acyltransferases can be used as synthetic biology tools to produce novel and potentially useful metabolites. ONE SENTENCE SUMMARY Analysis of Nicotiana glandular trichome metabolites and BAHD acyltransferases revealed diverse sucrose and glucose based acylesters.
Omicron BA.1, BA.2 and COVID-19 Booster Vaccination

TO THE EDITOR—In reply to the correspondence from Tjan et al [1] regarding the heterologous booster in healthy adults previously immunized with 2 doses of CoronaVac [2], the additional knowledge on immunogenicity of the booster (third dose) with BNT162b2 in BNT162b2primed individuals against the BA.2 omicron variant will help promote the vaccine uptake and coverage in themidst of a surge in BA.2 omicron worldwide. As of February 2022, the omicron variant was further classified into 4 main sublineages, BA.1, BA.1. 1, BA.2, and BA.3. Moreover, an epidemiological surveillance on coronavirus disease 2019 (COVID-19) showed that BA.2 sublineages have become the dominant variant globally [3]. In Thailand, the BA.2 sublineages have been detected since the end of January 2022. The proportion of BA.2 sublineages rapidly increased and accounted for more than 90% of positive cases reported in March 2022 [Puenpa J et al. unpublished]. Potent serum neutralizing antibody (nAbs) against BA.1 was observed after the heterologous booster in individuals previously immunized with 2 doses of CoronaVac [2]. Considering the waning immunity after primary series vaccination and the high transmissibility and potential immune escape of BA.2 sublineage, we further determined the immunogenicity of the mRNA-1273 booster against BA.1 and BA.2 in AZD1222-primed individuals using the 50% focus reduction neutralization test (FRNT50) as previously described [2].
Prevalence of Strongyloides stercoralis infection and associated clinical symptoms among schoolchildren living in different altitudes of Amhara National Regional State, northwest Ethiopia

Background Strongyloides stercoralis is a parasite that causes strongyloidiasis in humans. It is prevalent in the tropics and sub-tropics where poor sanitation is a common problem. The true prevalence of S. stercoralis in Ethiopia is underestimated due to the lack of a “Gold” standard diagnostic method. Moreover, its prevalence across altitudinal gradient in Amhara Region has not been studied. Methods A cross-sectional study was conducted among 844 schoolchildren in Amhara Region from April to December 2019. A stool sample was collected from each study participant and processed using formol ether concentration technique (FECT), spontaneous tube sedimentation technique (STST), Baermann concentration technique (BCT), agar plate culture (APC) and real-time polymerase chain reaction (RT-PCR). Data were entered using EpiData and analyzed by SPSS version 23 statistical software. Prevalence of S. stercoralis infection was determined using a single diagnostic technique and combination of techniques. Association of clinical variables with S. stercoralis infection was assessed by logistic regression and independent variables with p<0.05 were considered statistically significant. Results Prevalence of soil-transmitted helminths (STHs) and S. mansoni infections was 38.0% and 20.4%, respectively. Among STHs, the prevalence of hookworm infection was 32.8%. Prevalence of S. stercoralis infection was 39.0%, 28.8%, 10.9%, 10.3%, 4.0% and 2.0% by the respective, combinations of the five methods, RT-PCR, APC, BCT, STST and FECT. The highest prevalence rates, 48.2%, 45.0% and 41.1% of S. stercoralis were recorded in the age group of 12–14 years, males and rural dwellers, respectively. Prevalence rates of S. stercoralis infection in highland, semi-highland and lowland areas were 40.4%, 41.8% and 25.9%, respectively. Having abdominal pain (AOR = 2.48; 95% CI:1.65–3.72), cough (AOR = 1.63;95%CI:1.09–2.42), urticaria (AOR = 2.49;95%CI:1.50–4.01) and being malnourished (AOR = 1.44;95%:1.10–2.01) were significantly associated with strongyloidiasis. Conclusion Prevalence of S. stercoralis infection was high and varied across different altitudes in Amhara Region. Some clinical syndromes were found to be significantly associated with S. stercoralis infection. Therefore, proper diagnosis and preventive strategies against S. stercoralis infection are highly recommended to be devised and implemented in Amhara Region.
Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis

The roles of neutrophils in renal inflammation are currently unclear. On examining these cells in the unilateral ureteral obstruction murine model of chronic kidney disease, we found that the injured kidney bore a large and rapidly expanding population of neutrophils that expressed the eosinophil marker Siglec-F. We first verified that these cells were neutrophils. Siglec-F+ neutrophils were recently detected in several studies in other disease contexts. We then showed that a) these cells were derived from conventional neutrophils in the renal vasculature by TGF-β1 and GM-CSF; b) they differed from their parent cells by more frequent hypersegmentation, higher expression of profibrotic inflammatory cytokines, and notably, expression of collagen 1; and c) their depletion reduced collagen deposition and disease progression, but adoptive transfer increased renal fibrosis. These findings have thus unveiled a subtype of neutrophils that participate in renal fibrosis and a potentially new therapeutic target in chronic kidney disease.