Miracle-dz/UniFAR-FTUs huggingface dataset:
The apicoplast is important for the viability and persistence of 1 Toxoplasma gondii bradyzoites 2

16 Toxoplasma gondii is responsible for toxoplasmosis, a disease that can be serious when contracted 17 during pregnancy, but can also be a threat for immunocompromised individuals. Acute infection is 18 associated with the tachyzoite form that spreads rapidly within the host. However, under stress 19 conditions, some parasites can differentiate into cyst-forming bradyzoites, residing mainly in the 20 central nervous system, retina and muscle. Because this latent form of the parasite is resistant to 21 all currently available treatments, and is central to persistence and transmission of the parasite, 22 new specific therapeutic strategies targeting this developmental stage need to be discovered. 23 T. gondii contains a plastid of endosymbiotic origin called the apicoplast, which is an appealing 24 drug target because it is essential for tachyzoite viability and contains several key metabolic 25 pathways that are largely absent from the mammalian host. Its function in bradyzoites, however, is 26 unknown. Our objective was thus to study the contribution of the apicoplast to the viability and 27 persistence of bradyzoites during chronic toxoplasmosis.
A simple bypass assay for DNA polymerases shows that cancer‐associated hypermutating variants exhibit differences in vitro

Errors made by DNA polymerases contribute to both natural variation and, in extreme cases, genome instability and its associated diseases. Recently, the importance of polymerase misincorporation in disease has been highlighted by the identification of cancer‐associated polymerase variants with mutations in the exonuclease domain. A subgroup of these variants have a hypermutation phenotype in tumours, and when modelled in yeast, they show mutation rates in excess of that seen with polymerase with simple loss of proofreading activity. We have developed a bypass assay to rapidly determine the tendency of a polymerase to misincorporate in vitro. We have used the assay to compare misincorporation by wild‐type, exonuclease‐defective and two hypermutating human DNA polymerase ε variants, P286R and V411L. The assay clearly distinguished between the misincorporation rates of wild‐type, exonuclease dead and P286R polymerases. However, the V411L polymerase showed misincorporation rate comparable to the exonuclease dead enzyme rather than P286R, suggesting that there may be some differences in the way that these variants cause hypermutation. Using this assay, misincorporation opposite a templated C nucleotide was consistently higher than for other nucleotides, and this caused predominantly C‐to‐T transitions. This is consistent with the observation that C‐to‐T transitions are commonly seen in DNA polymerase ε mutant tumours.
Rido : clan feuding and conflict management in Mindanao

Survey of feuding families and clans in selected provinces in Mindanao / Jamail A. Kamlian -- Dynamics and management of rido in the Province of Maguindanao / Abhoud Syed M. Lingga -- Inventory of existing rido in Lanao del Sur, 1994-2004 / Moctar I. Matuan -- Management of clan conflict and rido among the Tausug, Magindanao, Maranao, Sama, and Yakan tribes / Ofelia L. Durante . [et al.] -- Responses to interkin group conflict in northern Mindanao / Erlinda Montillo-Burton . [et al.] -- Understanding inter-ethnic conflicts in north Cotabato and Bukidnon provinces / Guiamel Alim, Jose Bulao, Jr., and Ismael G. Kulat -- Management and resolution of rido among Meranao in Baloi, Lanao del Norte / Monalinda Emperio Doro -- Big war, small wars / Jose Jowel Canuday -- The celebrated cases of rido in Maguindanao and north Cotabato / United Youth for Peace and Development (UNYPAD) -- Tausug and Corsican clan feuding / Gerard Rixhon.
Impact of Dementia on Incidence and Severity of Postoperative Pulmonary Complications Following Hip Fracture Surgery Among Older Patients

Postoperative pulmonary complications (PPCs) are the leading cause of death following hip fracture surgery. Dementia has been identified as a PPC risk factor that complicates the clinical course. By leveraging electronic health records, this retrospective observational study evaluated the impact of dementia on the incidence and severity of PPCs, hospital length of stay, and postoperative 30-day mortality among 875 older patients (≥65 years) who underwent hip fracture surgery between October 1, 2015 and December 31, 2018 at a health system in the southeastern United States. Inverse probability of treatment weighting using propensity scores was utilized to balance confounders between patients with and without dementia to isolate the impact of dementia on PPCs. Regression analyses revealed that dementia did not have a statistically significant impact on the incidence and severity of PPCs or postoperative 30-day mortality. However, dementia significantly extended the hospital length of stay by an average of 1.37 days.
Generating designs for comparative experiments with two blocking factors

Often, comparative experiments involve a single treatment factor and two blocking factors, for example, augmented row–column, two‐phase, and incomplete row–column experiments. These experiments are widely used in agriculture. Finding good designs for these experiments is a major challenge when the number of treatments is large and the blocking structure is complex. In this paper, we first propose a new search algorithm that is combined with efficient update formulae, so that optimal designs with two blocking factors can be found within a reasonable time. Second, we compare augmented row–column designs generated with our new method to those obtained from CycDesigN, DiGGer, and the OPTEX procedure of SAS in terms of computing times as well as the quality of solutions. Third, we illustrate our proposed approach with four applications. We show an example where our efficient update formulae work while existing update formulae cannot be applied, and we use our search framework to generate augmented row–column, two‐phase, and incomplete row–column designs. We end the paper with a conclusion along with suggestions for potential applications.
Metabolism and Excretion of Therapeutic Peptides: Current Industry Practices, Perspectives, and Recommendations

Therapeutic peptides (TPeps) have expanded from the initial endogenous peptides to complex modified peptides through medicinal chemistry efforts for almost a century. Different from small molecules and large proteins, the diverse submodalities of TPeps have distinct structures and carry different absorption, distribution, metabolism, and excretion (ADME) properties. There is no distinct regulatory guidance for the industry on conducting ADME studies (what, how, and when) for TPeps. Therefore, the Peptide ADME Working Group sponsored by the Translational and ADME Sciences Leadership Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) was formed with the goal to develop a white paper focusing on metabolism and excretion studies to support discovery and development of TPeps. In this paper, the key learnings from an IQ industry survey and U.S. Food and Drug Administration/European Medicines Agency submission documents of TPeps approved between 2011 and 2022 are outlined in detail. In addition, a comprehensive assessment of in vitro and in vivo metabolism and excretion studies, mitigation strategies for TPep metabolism, analytical tools to conduct studies, regulatory status, and Metabolites in Safety Testing considerations are provided. Finally, an industry recommendation on conducting metabolism and excretion studies is proposed for regulatory filing of TPeps. SIGNIFICANCE STATEMENT This white paper presents current industry practices for metabolism and excretion studies of therapeutic peptides based on an industry survey, regulatory submission documents, and expert opinions from the participants in the Peptide Absorption, Distribution, Metabolism, and Excretion Working Group of the International Consortium for Innovation and Quality in Pharmaceutical Development. The group also provides recommendations on the Metabolites in Safety Testing considerations and metabolism and excretion studies for regulatory filing of therapeutic peptides.
Dehalococcoides mccartyi strain NIT01 grows more stably in vessels made of pure titanium rather than the stainless alloy SUS304

Abstract Advances in many isolation studies have revealed that pure Dehalococcoides grow stably, although the large‐scale pure cultivation of Dehalococcoides has yet to be established. In this study, 7 L‐culturing of Dehalococcoides mccartyi strain NIT01 was first performed using vessels made of glass and stainless alloy SUS304. All batches cultured in the glass vessel successfully dechlorinated >95% of 1 mM trichloroethene (TCE) to ethene (ETH), whereas only 5 out of 13 batches cultured in the SUS304 vessel did the same. The difference in dechlorination efficiency suggested the possible inhibition of dechlorination by SUS304. Also, the strain NIT01 showed long delays in dechlorination with pieces of SUS316, steel, and a repeatedly used SUS304, but not with titanium. The repeatedly used SUS304 cracked and increased the Fe2+ concentration to ≥76 μM. Dechlorination by this strain was also inhibited with ≥1000 μM Fe2+ and ≥23 μM Cr3+ but not with ≤100 μM Ni2+, suggesting that Cr3+ eluted from solid stainless alloys inhibited the dechlorination. Culturing in a titanium vessel instead of a stainless alloy showed the complete dechlorination of 1 mM TCE within 12–28 days with a growth yield of 2.7 × 107 cells/μmol‐released Cl−, even after repeating use of the vessels six times.
Phosphorylation of RhoGDI1, a Rho GDP dissociation inhibitor, regulates root hair development in Arabidopsis under salt stress

Significance Plants must actively regulate their growth to acclimate to stressful environments and optimize growth. Here, we describe a mechanism by which a root hair–specific response is important for salt tolerance in seedlings. We determined that SALT OVERLY SENSITIVE 2 (SOS2), a kinase that acts as a key master regulator in salt resistance, participates in root hair development under salt stress via a mechanism involving phosphorylation of (GUANOSINE NUCLEOTIDE DIPHOSPHATE DISSOCIATION INHIBITOR 1) RhoGDI1. We further demonstrated that the SOS2–RhoGDI1–ROP2 (SOS2–RhoGDI1–Rho GTPASE OF PLANTS 2) module regulates root hair initiation and growth to provide plant salt tolerance.
Minimum 10-Year Clinical Outcomes and Survivorship of Meniscal Allograft Transplantation With Fresh-Frozen Allografts Using the Bridge-in-Slot Technique

Background: Meniscal allograft transplantation (MAT) has been shown to provide clinical benefits in patients with symptomatic meniscal deficiency in the short term and midterm. There is, however, a paucity of data regarding long-term outcomes after MAT using fresh-frozen allografts and the bridge-in-slot technique. Purpose: To report clinical outcomes and revision rates after primary MAT with fresh-frozen allografts and the bridge-in-slot technique in a large case series of patients at a 10-year minimum follow-up. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review of prospectively collected data was performed on patients undergoing primary MAT between 2001 and 2012. Lysholm, International Knee Documentation Committee subjective form, and Knee injury and Osteoarthritis Outcome Score subscales were collected preoperatively and at 1-, 2-, 5-, and minimum 10-year follow-ups. Cox proportional hazards modeling was used to identify variables associated with reoperation and failure, defined as revision MAT or conversion to arthroplasty. Reoperation was defined as a subsequent surgical intervention on the transplanted meniscus, including partial or total meniscectomy, meniscal repair, or failure as defined in the previous sentence. Results: A total of 174 patients undergoing MAT met the inclusion criteria and were followed for a mean of 12.7 ± 2.7 years (range, 10.0-21.0 years). The mean age at surgery was 28.3 ± 10.1 years. The patients were predominantly female (n = 92; 53%), and medial MAT was the most commonly performed procedure (n = 91; 52%). Concomitant procedures were performed in 115 patients (66%), with the most common procedure being osteochondral allograft transplantation (n = 59; 34%). Patients demonstrated statistically significant postoperative improvements at all time points for all patient-reported outcome measures (P≤ .0001). A total of 65 patients (37%) underwent a meniscal reoperation at a mean time of 6.6 ± 5.5 years (range, 0.3-16.7 years) postoperatively. A total of 40 patients (23%) met the criteria for failure at a mean time of 7.3 ± 5.0 years (range, 1.0-17.4 years) after MAT, with 22 of these patients having undergone a previous meniscal reoperation. At the final follow-up, 13 patients (7%) had undergone revision MAT and 27 (15%) had converted to arthroplasty. The MAT survival rates free of meniscal reoperation and failure were 73% and 85% at 10 years and 60% and 72% at 15 years, respectively. At the time of the final follow-up, 86% of patients reported that they were satisfied with their overall postoperative condition. Conclusion: Primary MAT demonstrates efficacy and durability with high rates of patient satisfaction at a minimum 10-year follow-up. Patients should be counseled that although reoperation rates may approach 40% at 15 years, rates of overall revision MAT and conversion to arthroplasty remain low at long-term follow-up.
A Rational Design of Isoindigo‐Based Conjugated Microporous n‐Type Semiconductors for High Electron Mobility and Conductivity

The development of n‐type organic semiconductors has evolved significantly slower in comparison to that of p‐type organic semiconductors mainly due to the lack of electron‐deficient building blocks with stability and processability. However, to realize a variety of organic optoelectronic devices, high‐performance n‐type polymer semiconductors are essential. Herein, conjugated microporous polymers (CMPs) comprising isoindigo acceptor units linked to benzene or pyrene donor units (BI and PI) showing n‐type semiconducting behavior are reported. In addition, considering the challenges of deposition of a continuous and homogeneous thin film of CMPs for accurate Hall measurements, a plasma‐assisted fabrication technique is developed to yield uniform thin films. The fully conjugated 2D networks in PI‐ and BI‐CMP films display high electron mobility of 6.6 and 3.5 cm2 V−1 s−1, respectively. The higher carrier concentration in PI results in high conductivity (5.3 mS cm−1). Both experimental and computational studies are adequately combined to investigate structure–property relations for this intriguing class of materials in the context of organic electronics.
Distribution of Wind-Induced Turbulent Mixing in the Ocean

tion of diapycnal diffusivity below 1000m depth. Although wind stress fluctuation is a candidate for major energy sources of diapycnal mixing processes, the global distribution of wind-induced diapycnal diffusivity is still uncertain. It has been believed that internal waves generated by wind stress fluctuations at middle and high latitudes propagate equatorward until their frequency is twice the local inertial frequency and break down via parametric subharmonic instabilities causing diapycnal mixing. In order to check the proposed scenario, using a vertically two-dimensional primitive equation model, we examine the spatial distribution of "mixing hotspots" caused by wind stress fluctuations. It is shown that most of the wind-induced energy fed into the ocean interior is dissipated within the top 1000m depth in the wind-forced area and the energy dissipation rate at low latitudes is very small. Consequently, the energy supplied to diapycnal mixing processes below 1000m depth falls short of the value required to sustain the global ocean overturning circulation.
SNTB1 regulates colorectal cancer cell proliferation and metastasis through YAP1 and the WNT/β-catenin pathway

ABSTRACT Colorectal cancer is a common type of digestive tract cancer with a significant morbidity and death rate across the world, partially attributing to the metastasis-associated problems. In this study, integrative bioinformatics analyses were performed to identify genes that might contribute to colorectal cancer metastasis, and 293 genes were dramatically increased and 369 genes were decreased within colon cancer samples. Among up-regulated genes, top five genes correlated with colorectal cancer patient’s prognosis were verified for expression in clinical samples and syntrophin beta 1 (SNTB1) was the most up-regulated. In vitro, SNTB1 knockdown suppresses the malignant behaviors of colorectal cancer cells, including cell viability, colony formation capacity, as well as the abilities to migrate and invade. Furthermore, SNTB1 knockdown decreased the levels of Wnt1, C-Jun, C-Myc, TCF7, and cyclin D1, and inhibited EMT in both cell lines. In vivo, SNTB1 knockdown inhibited tumor growth and metastasis in nude mice models. SNTB1 positively regulated Yes1 associated transcriptional regulator (YAP1) expression; YAP1 partially reversed the effects of SNTB1 on colorectal cancer cell phenotypes and the Wnt/β-catenin/MYC signaling. In conclusion, SNTB1 knockdown inhibits colorectal cancer cell aggressiveness in vitro and tumor growth and metastasis in vivo through the Wnt/β-catenin/MYC signaling; YAP1 might mediate SNTB1 functions on colorectal cancer.
Cohesin contributes to transcriptional repression of stage‐specific genes in the human malaria parasite

The complex life cycle of the human malaria parasite, Plasmodium falciparum, is driven by specific transcriptional programs, but it is unclear how most genes are activated or silenced at specific times. There is an association between transcription and spatial organization; however, the molecular mechanisms behind genome organization are unclear. While P. falciparum lacks key genome‐organizing proteins found in metazoans, it has all core components of the cohesin complex. To investigate the role of cohesin in P. falciparum, we functionally characterize the cohesin subunit Structural Maintenance of Chromosomes protein 3 (SMC3). SMC3 knockdown during early stages of the intraerythrocytic developmental cycle (IDC) upregulates a subset of genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP‐seq analyses reveal that during the IDC, SMC3 enrichment at the promoter regions of these genes inversely correlates with gene expression and chromatin accessibility. These data suggest that SMC3 binding contributes to the repression of specific genes until their appropriate time of expression, revealing a new mode of stage‐specific gene repression in P. falciparum.
Affordable, accurate and unbiased RNA sequencing by manual library miniaturization: A case study in barley

Summary We present an easy‐to‐reproduce manual miniaturized full‐length RNA sequencing (RNAseq) library preparation workflow that does not require the upfront investment in expensive lab equipment or long setup times. With minimal adjustments to an established commercial protocol, we were able to manually miniaturize the RNAseq library preparation by a factor of up to 1:8. This led to cost savings for miniaturized library preparation of up to 86.1% compared to the gold standard. The resulting data were the basis of a rigorous quality control analysis that inspected: sequencing quality metrics, gene body coverage, raw read duplications, alignment statistics, read pair duplications, detected transcripts and sequence variants. We also included a deep dive data analysis identifying rRNA contamination and suggested ways to circumvent these. In the end, we could not find any indication of biases or inaccuracies caused by the RNAseq library miniaturization. The variance in detected transcripts was minimal and not influenced by the miniaturization level. Our results suggest that the workflow is highly reproducible and the sequence data suitable for downstream analyses such as differential gene expression analysis or variant calling.
Hesitancy toward vaccination against COVID-19: A scoping review of prevalence and associated factors in the Arab world

ABSTRACT Despite widespread availability of vaccines against SARS-CoV-2 virus, the cause of Coronavirus Disease 2019 (COVID-19), its uptake in many Arab countries is relatively low. This literature review aimed to scope evidence on COVID-19 vaccine hesitancy (VH) in the Arab world. A total of 134 articles reporting prevalence of COVID-19 VH and associated factors, conducted in any of the 22 Arab League countries, were reviewed. COVID-19 VH prevalence ranged from 5.4% to 83.0%. Female gender, young age, low education level and lack of previous influenza vaccine uptake were most commonly reported to be associated with COVID-19 VH. The most-reported personal concerns contributing toward VH were related to the rapid development, safety and side effects of vaccine, as well as an overall lack of trust in government policies toward pandemic control and widespread conspiracy theories. Tailored interventions to enable the distribution of trusted information and enhance public acceptance of immunization are warranted.
A systematic review of the evidence on the associations and safety of COVID-19 vaccination and post COVID-19 condition

Abstract Post COVID-19 condition (PCC) refers to persistent or recurring symptoms (>8 weeks) occurring ≤12 weeks following acute COVID-19. The objective of this systematic review was to assess the evidence on the risk of PCC with vaccination before or after COVID-19 or after developing PCC, and the safety of vaccination among those already experiencing PCC. A search was conducted up to 13 December 2022 and standard systematic review methodology was followed. Thirty-one observational studies were included. There is moderate confidence that two doses of vaccine given pre-infection reduced the odds of PCC (pooled OR (pOR) 0.67, 95% CI 0.60–0.74, I2 = 59.9%), but low confidence that one dose may not reduce the odds (pOR 0.64, 95% CI 0.31#x2013;1.31, I2 = 99.2%), and the evidence is very uncertain about the effect of three doses (pOR 0.45, 95% CI 0.10#x2013;1.99, I2 = 30.9%). One of three studies suggested vaccination shortly after COVID-19 may offer additional protection from developing PCC compared to unvaccinated individuals, but this evidence was very uncertain. For those with PCC, vaccination was not associated with worsening PCC symptoms (10 studies) and appears safe (3 studies), but it is unclear if vaccination may change established PCC symptoms.
Preliminary findings on long‐term effects of fMRI neurofeedback training on functional networks involved in sustained attention

Neurofeedback based on functional magnetic resonance imaging allows for learning voluntary control over one's own brain activity, aiming to enhance cognition and clinical symptoms. We previously reported improved sustained attention temporarily by training healthy participants to up‐regulate the differential activity of the sustained attention network minus the default mode network (DMN). However, the long‐term brain and behavioral effects of this training have not yet been studied. In general, despite their relevance, long‐term learning effects of neurofeedback training remain under‐explored.