bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals
Authors: Nka Alex Durand , Bouba Yagai , Teto Georges , Semengue Ezéchiel Ngoufack Jagni , Takou Désiré Komego , Ngueko Aurelie Minelle Kengni , Fabeni Lavinia , Carioti Luca , Armenia Daniele , Pabo Willy , Dambaya Béatrice , Sosso Samuel Martin , Colizzi Vittorio , Perno Carlo-Federico , Ceccherini-Silberstein Francesca , Santoro Maria Mercedes , Fokam Joseph , Ndjolo Alexis 
Published: November 2022

Abstract

Objectives
We evaluated the HIV-1 capsid genetic variability and lenacapavir drug resistance-associated mutations (DRMs) among drug-naive individuals across HIV-1 clades.

Methods
A total of 2031 HIV-1 sequences from drug-naive patients were analysed for capsid amino acid modification and the prevalence of lenacapavir DRMs. Amino acid positions with &lt;5% variability were considered as conserved and variability was analysed by HIV-1 clades.

Results
Overall, 63% (148/232) of amino acid positions were conserved in the capsid protein. Of note, conservation was consistent in specific binding residues of cellular factors involved in viral replication [CypA (G89, P90), CPSF6 (Q4, N57, N74, A77, K182) and TRIM-NUP153 (R143)], while N183 (12.31%) was the only non-conserved lenacapavir binding residue. The overall prevalence (95% CI) of lenacapavir DRMs was 0.14% (0.05–0.44) (3/2031), with M66I (0.05%) and Q67H (0.05%) observed in subtype C, and T107N (0.05%) observed in CRF01_AE. Moreover, polymorphic mutations M66C (n = 85; 4.18%), Q67K (n = 78; 3.84%), K70R (n = 7; 0.34%), N74R (n = 57; 2.81%) and T107L (n = 82; 4.03%) were observed at lenacapavir resistance-associated positions.

Conclusions
The low level of lenacapavir DRMs (&lt;1%) supports its predicted effectiveness for treatment and prevention, regardless of HIV-1 clades. The established conserved regions hence serve as a hallmark for the surveillance of novel mutations potentially relevant for lenacapavir resistance.
Chinese Import Competition and Gendered Labor Market Outcomes: Evidence from Ethiopian Firm-Level Data
Authors: Afesorgbor Sylvanus Kwaku , Acquah Ruby Elorm , Ayele Yohannes 
Published: November 2022

Abstract
In this paper, we analyse the relationship between Chinese import competition and gendered labor market outcomes within the context of a developing country. To do this, we merge a rich manufacturing firm-level panel data set from Ethiopia with trade data covering the years 1997–2010. Thus, we map out the effect of trade shocks from import surges on labor force participation and compensation, decomposed by gender. Results from the study show that rising import competition from China had a heterogeneous effect on female and male labor market outcomes. Import competition from China is associated with a negative and statistically significant effect on female employment, but not male employment. Looking at workers’ occupation, we find that for production workers import competition is adversely related with female employment outcomes while there is no statistically significant association with employment of administrative workers. For wage inequality, male wages in general are negatively associated with import competition, while we found no effect on female wages.
Availability of aldo-keto reductase 1C3 and ATP-binding cassette B1 as therapeutic targets for alleviating paclitaxel resistance in breast cancer MCF7 cells
Authors: Matsunaga Toshiyuki , Horinouchi Misato , Saito Haruhi , Hisamatsu Aki , Iguchi Kazuhiro , Yoshino Yuta , Endo Satoshi , Ikari Akira 
Published: November 2022

AbstractPaclitaxel (PTX) is frequently utilized for the chemotherapy of breast cancer, but its continuous treatment provokes hyposensitivity. Here, we established a PTX-resistant variant of human breast cancer MCF7 cells and found that acquiring the chemoresistance elicits a remarkable up-regulation of aldo-keto reductase (AKR) 1C3. MCF7 cell sensitivity to PTX toxicity was increased by pretreatment with AKR1C3 inhibitor and knockdown of this enzyme, and decreased by its overexpression, inferring a crucial role of AKR1C3 in the development of PTX resistance. The PTX-resistant cells were much less sensitive to 4-hydroxy-2-nonenal and acrolein, cytotoxic reactive aldehydes derived from ROS-mediated lipid peroxidation, compared with the parental cells. Additionally, the resistant cells lowered levels of 4-hydroxy-2-nonenal formed during PTX treatment, which was mitigated by pretreating with AKR1C3 inhibitor, suggesting that AKR1C3 procures the chemoresistance through facilitating the metabolism of the cytotoxic aldehyde. The gain of PTX resistance additively promoted the aberrant expression of an ATP-binding cassette (ABC) transporter ABCB1 among the ABC transporter isoforms. The combined treatment with AKR1C3 and ABCB1 inhibitors overcame the PTX resistance and cross-resistance to another taxane-based drug docetaxel. Collectively, combined treatment with AKR1C3 and ABCB1 inhibitors may exert an overcoming effect of PTX resistance in breast cancer.
Liposomal irinotecan with fluorouracil and leucovorin after gemcitabine-based therapy in Japanese patients with metastatic pancreatic cancer: additional safety analysis of a randomized phase 2 trial
Authors: Furuse Junji , Ueno Makoto , Ikeda Masafumi , Okusaka Takuji , Teng Zhaoyang , Furuya Momoko , Ioka Tatsuya 
Published: November 2022

Abstract

Background
Nanoliposomal irinotecan (nal-IRI) was recently authorized in Japan for unresectable pancreatic cancer after disease progression following chemotherapy. Physicians now consider certain aspects of nal-IRI safety profile as slightly different from conventional irinotecan. This report aims to explore additional aspects of the nal-IRI safety in Japanese phase 2 study.

Methods
We analyzed the incidence, time to first onset, and time to resolution for adverse events that require special attention and other selected toxicities in the nal-IRI combination group (n = 46).

Results
Leukopenia/neutropenia (76.1%/71.7%), diarrhea (58.7%) and hepatic dysfunction (41.3%) were the most commonly reported treatment-emergent adverse events, with a median time to onset of 21.0 days (range: 8, 97), 9.0 days (1, 61) and 22.0 days (2, 325), respectively, and a median time to resolution of 8.0 days (95% confidence intervals: 8, 9), 4.0 days (4, 8) and 40.0 days (9, –), respectively. Eight patients experienced Grade ≥ 3 diarrhea and their symptoms were well controlled by dose modification except one patient who had drug withdrawal. The median time to resolution for Grade ≥ 3 and Grade ≤ 2 diarrhea was 17.5 days (95% confidence intervals: 1, 31) and 4 days (3, 7), respectively. Anorexia occurred in 28/46 patients (60.9%) with a median time to onset of 4.0 days (range: 2, 132) and a median time to resolution of 12.0 days (95% confidence intervals: 6, 26).

Conclusions
We explored safety profile of nal-IRI combination regimen recognized as effective and tolerable treatment for Japanese unresectable pancreatic cancer patients. Although the treatment-emergent adverse events occurred were controllable, patients with prolonged toxicities should be closely managed.
Idiopathic parotid pain: a rare clinical presentation of first bite syndrome without history of head and neck surgery or underlying malignancies
Authors: Saleem Matthew I , Bhuiya Sabreen , Tham Tristan , Georgolios Alexandros 
Published: November 2022

Abstract
First bite syndrome (FBS) has been previously characterised as a surgical complication, following head and neck surgical procedures. There are also rare reports in the literature associating FBS with malignancies of the head and neck. The term ‘idiopathic parotid pain’ (IPP) has been used recently to describe an exceedingly rare clinical presentation similar to FBS, but without history of head and neck surgery or malignancy. We present the rare case of a 65-year-old male diagnosed with IPP, our work-up and management.
Establishment of a gene recombination method for a major human skin commensal fungus, Malassezia restricta, using Agrobacterium tumefaciens-mediated gene transfer system
Authors: Cho Otomi , Matsumoto Yasuhiko , Yamada Tsuyoshi , Sugita Takashi 
Published: November 2022

Abstract
Malassezia restricta is the most predominant fungus in the microbiome of human skin. This microorganism can cause or exacerbate Malassezia-associated skin dermatitis, seborrheic dermatitis, atopic dermatitis, and pityriasis versicolor. The virulence factors of M. restricta have not been analyzed because a gene recombination system has not been developed. In this study, we established an Agrobacterium tumefaciens-mediated gene transfer (ATMT) system, optimized for generating gene-deficient mutants of M. restricta. A mutant of FKB1 gene, which encodes the FKBP12 protein that binds to the calcineurin inhibitor tacrolimus, was generated using the ATMT system. Subsequently, the FKB1 gene was reintroduced into the FKB1 gene-deficient mutant for obtaining a gene-complemented strain. The wild-type strain of M. restricta was sensitive to tacrolimus, whereas the FKB1 gene-deficient mutant was resistant to tacrolimus; the phenotypic drug susceptibility in the mutant was restored by reintroducing the FKB1 gene. Contrastingly, the FKB1 gene-deficient mutant was not resistant to cyclosporine A, which also inhibits calcineurin by binding to cyclophilin A. The gene recombination system for M. restricta will facilitate in elucidating the molecular mechanisms causing Malassezia-associated dermatitis.
Fair Market Constitutionalism: From Neo-liberal to Democratic Liberal Economic Governance
Authors: Dixon Rosalind 
Published: November 2022

Abstract
Neo-liberalism was in crisis well before COVID-19; and COVID-19 has only further highlighted the gaps and fault lines in existing liberal democratic models. But this does not mean that we should walk away from liberal ideals, or the general idea of globalisation or market-based forms of ordering. Instead, we should seek a new, more ‘democratic’ or pro-social understanding of the liberal ideal, which emphasises the idea of fair rather over free markets. This idea of fair markets can be understood in numerous ways, but I suggest that it is best understood as entailing a commitment by the state to: (i) guaranteeing access to a public baseline of core goods, or access to a generous social minimum to all citizens, regardless of market outcomes; (ii) ensuring equality of access to certain ‘relative goods’; (iii) regulating market power or sources of monopoly power; and (iv) responding to or ‘internalising’ negative externalities or social costs associated with private market behaviour. The article explores what this entails for the design of constitutions, and especially constitutional property and social rights, and the scope and strength of judicial review. Ultimately, the article suggests, fair market constitutionalism points to the desirability of a combination of weak property and social rights—ie property rights that offer some but not complete protection for existing economic entitlements, coupled with legislative duties to implement fair market norms or limited weak social rights guarantees. But this does not mean that such guarantees can only be weakly enforced by courts: blockages in the democratic process may mean that courts can and should adopt a weak–strong—or responsive—approach to enforcing these fundamentally weak rights guarantees.
Conflict misperceptions between citizens and foreigners across the globe
Authors: Romano Angelo , Gross Jörg , De Dreu Carsten K W 
Published: November 2022

AbstractIn a globalizing world, conflict between citizens and foreigners hinders cooperation and hampers how well the global community can tackle shared problems. Here, we study conflict between citizens and foreigners and find that people substantially misperceive how competitive foreigners are. Citizens (from 51 countries; N = 12,863; 656,274 decisions) interacted with foreigners in incentivized contest experiments. People across the globe systematically failed to anticipate the competitiveness of foreigners and either competed too much or too little. Competition was poorly explained by differences in cultural values or environmental stress. By contrast, competition and concomitant conflict misperceptions were robustly accounted for by differences in the wealth of nations, institutions, and histories of engaging in international conflict. Our results reveal how macro-level socio-economic differences between countries create false stereotypes and might breed conflict.
Neuropathic upper extremity pain
Authors: Worthley Elizabeth 
Published: November 2022

ABSTRACT
Neuropathic upper extremity pain has many causes. Cubital tunnel syndrome is the second most common compressive peripheral neuropathy after carpal tunnel syndrome. Entrapment, or compression, of the ulnar nerve at the elbow classically presents with elbow pain, numbness in the ulnar nerve distribution, and weakness in the hand. C8 radiculopathy and various brachial plexopathies can mimic cubital and carpal tunnel syndromes. Neoplastic brachial plexopathy typically is caused by local extension of a primary or metastatic tumor into the brachial plexus. Double-crush syndrome further complicates neuropathic upper extremity pain. This case report describes a patient with a double-crush lesion involving the ulnar nerve at the elbow and a metastatic mass involving the lower trunk of the brachial plexus. Because of overlapping symptoms and presentations of several upper extremity nerve conditions, clinicians must perform a thorough history and physical examination and understand the sensory and motor innervation of the upper extremity to arrive at a timely and accurate diagnosis.
A review of slipped capital femoral epiphysis
Authors: Cotton Emma V. , Fowler Samuel C. , Maday Kristopher R. 
Published: November 2022

ABSTRACT
Hip pain in children is common, with causes ranging from the benign to destructive. This article reviews slipped capital femoral epiphysis (SCFE), one of the most common hip pathologies in preadolescents and adolescents, which often is missed or delayed in diagnosis because of its vague, atypical presentation.
Complicated appendicitis in a patient with myelodysplastic syndrome and pancytopenia
Authors: Gaffney Samantha , Dunson William 
Published: November 2022

ABSTRACT
Patients with immunocompromise presenting with abdominal pain can present a diagnostic challenge, because they may have atypical or vague symptoms. This case report discusses nonoperative management of a patient with immunocompromise, complicated appendicitis, and intra-abdominal infection.
Impact of a Standardized Nutrition Bundle Including Donor Human Milk on Hospital Outcomes in Very Low Birth-Weight (VLBW) Infants in a Safety-Net Hospital
Authors: Stefanescu Beatrice M. , Camacho Jenny , Stefanescu Andrei R. , DuPont Tara , Leung Rachel 
Published: November 2022

Background:
Standardized protocols have been shown to reduce clinical practice variation and improve patient outcomes.

Purpose:
To measure the impact of a standardized nutrition bundle inclusive of donor human milk (DHM) on hospital outcomes of very low birth-weight (VLBW) infants in a safety-net hospital.

Methods:
The study used the Model for Improvement methodology to drive improvement in practice. Outcome measures consisted of necrotizing enterocolitis (NEC), mortality, growth at 36 weeks' postmenstrual age and discharge, as well as volume and type of milk consumption during hospitalization.

Findings:
NEC rate decreased from 16.67% in the control group to 6.78% in the standardized nutrition bundle group (P = .07). Similarly, there was significant reduction in mortality with the bundled intervention (15.6% in the control group vs 1.6% in the nutrition bundle group; P = .006). Time to first (15 vs 27.5 hours of life; P < .001) and full-volume enteral feeding (8.5 vs 10 days; P = .086) were reduced in the standardized nutrition bundle group compared with the control group. The human milk volume almost doubled with the intervention.

Implications for Practice:
Our standardized nutrition bundle protocol inclusive of DHM resulted in lower NEC rates and reduced mortality. The implementation of the DHM program proved to be cost-effective and saved lives. Our findings may help guide development of a structured approach to nutrition protocols inclusive of DHM that can be adapted by other units located in safety-net hospitals.

Implications for Research:
Future research on ethnic and racial barriers to access and affordability of DHM is warranted and much needed.
Evaluation of 5 Fraction Stereotactic Body Radiation Therapy (SBRT) for Osseous Renal Cell Carcinoma Metastases
Authors: Dove Austin P.H. , Wells Alex , Gong Wu , Liu Dandan , Kirschner Austin N. 
Published: November 2022

Objectives:
The best fractionation for stereotactic body radiotherapy (SBRT) in renal cell carcinoma (RCC) metastases has not been well defined. In addition, the literature on outcomes using 5-fraction SBRT in the setting of osseous metastases has not been well reported.

Materials and Methods:
Thirty-nine patients with 69 RCC osseous metastases were treated using 5-fraction SBRT at a single institution using 2 dose-fractionation schemes. Overall survival and local-control (LC) outcomes of the 2 fractionation schemes were studied using Kaplan-Meier curves.

Results:
Of the 69 lesions included in the study, 20 were treated with 30 grays (Gy) in 5 fractions and 49 were treated with 40 Gy in 5 fractions. The median age of patients at diagnosis was 58.4 years. The 1-year LC rate for all treated lesions was 85.5% (59/69) with an LC of 90% (18/20) for lesions receiving 30 Gy and 83.7% (41/49) in lesions receiving 40 Gy. There was no statistically significant difference in 1-year LC rate between the 2 fractionation schemes (P-value, 0.553).

Conclusions:
Patients with osseous RCC metastases undergoing 5 fractions of SBRT had favorable LC outcomes. There was no difference in survival or LC between the 40 Gy and 30 Gy treatment arms.
Caring for Atypical Wounds in Patients With Severe Obesity
Authors: Ciabattoni Matthew , Ward Amanda C. , Preston Ave Maria 
Published: November 2022

BACKGROUND:
The prevalence of obesity has grown over the past several decades. It exerts a negative effect on multiple body systems, including the integumentary system, and it increases the risk for development of chronic diseases. Caring for hospitalized patients with severe obesity presents unique challenges, especially when wounds are present.

CASES:
This article reviews 3 patients with severe obesity hospitalized with extensive full-thickness lower extremity wounds. In all 3 cases, the wounds were comparable to the presentation and evolution of a typical deep tissue pressure injury. In addition, none of the wounds were classified as pressure injuries. These extensive wounds seen in patients with severe obesity lack a clear etiology and pathophysiology, but present wound care nurses and other care providers with unique challenges well beyond evidence-based principles for selection of appropriate topical care.

CONCLUSION:
These cases illustrate lessons learned when caring for 3 patients during several months of hospitalization at a large academic medical center. Additional research is needed to enhance our knowledge of the etiology of these wounds, especially since the population of patients with severe obesity has become more prevalent.
Single-Cell ATAC-seq analysis via Network Refinement with peaks location information
Authors: Yu Jiating , Sun Duanchen , Hou Zhichao , Wu Ling-Yun 
Published: November 2022

AbstractSingle-cell ATAC-seq (scATAC-seq) data provided new insights into the elaboration of cellular heterogeneity and transcriptional regulation. However, scATAC-seq data posed challenges for data analysis because of its near binarization, high sparsity, and ultra-high dimensionality properties. Here we proposed a novel network diffusion-based method to comprehensively analyze scATAC-seq data, namedSingle-CellATAC-seq Analysis via NetworkRefinement withPeaks Location Information (SCARP). By modeling the prior probability of co-accessibility between adjacent peaks as a decreasing function of genomic distance, SCARP is the first scATAC-seq analysis method that utilizes the genomic information of peaks, which contributed to characterizing co-accessibility of peaks. SCARP used network to model the accessible relationships between cells and peaks, aggregated information with the diffusion method, and then performed dimensionality reduction to obtain low-dimensional cell embeddings as well as peak embeddings. We have demonstrated through sufficient experiments that SCARP facilitated superior analysis of scATAC-seq data. Specifically, SCARP exhibited outstanding cell clustering performance to better elucidate cell heterogeneity, and can be used to reveal new biologically significant cell subpopulations. SCARP was also instrumental in portraying co-accessibility relationships of accessible regions and providing new insight into transcriptional regulation, and those SCARP-derived genes were involved in some key KEGG pathways related to diseases. To sum up, our studies suggested that SCARP is a promising tool to comprehensively analyze the scATAC-seq data from a new perspective.
Alterations inPTPN11and other RAS-/MAP-Kinase pathway genes define ganglioglioma with adverse clinical outcome and atypic histopathological features
Authors: Hoffmann Lucas , Coras Roland , Kobow Katja , López-Rivera Javier A. , Lal Dennis , Leu Costin , Najm Imad , Nürnberg Peter , Herms Jochen , Harter Patrick N. , Bien Christian G. , Kalbhenn Thilo , Müller Markus , Pieper Tom , Hartlieb Till , Kudernatsch Manfred , Hamer Hajo , Brandner Sebastian , Rössler Karl , Blümcke Ingmar , Jabari Samir 
Published: November 2022

AbstractThePTPN11gene was recently described as a novel lesional epilepsy gene by extensive exome-wide sequencing studies. However, germline mutations ofPTPN11and otherRAS-/MAP-Kinase signaling pathwaygenescause Noonan syndrome, a multisystem disorder characterized by abnormal facial features, developmental delay, and sporadically, also brain tumors. Herein, we performed a deep phenotype-genotype analysis of a comprehensive series of ganglioglioma (GG) with brain somatic alterations of thePTPN11gene compared to GG with other common MAP-Kinase signaling pathway alterations. Seventy-two GG were submitted to whole exome sequencing and genotyping and 86 low grade epilepsy associated tumors (LEAT) to DNA-methylation analysis. Clinical data were retrieved from hospital files including postsurgical disease onset, age at surgery, brain localization, and seizure outcome. A comprehensive histopathology staining panel was available in all cases. We identified eight GG withPTPN11alterations, copy number variant (CNV) gains of chromosome 12, and the commonality of additional CNV gains inFGFR4, RHEB, NF1, KRASas well asBRAFV600Ealterations. Histopathology revealed an atypical and complex glio-neuronal phenotype with subpial tumor spread and large, pleomorphic, and multinuclear cellular features. Only three out of eight patients with GG andPTPN11alterations were free of disabling-seizures two years after surgery (38% Engel I). This was remarkably different from our series of GG withBRAFV600Emutations (85% Engel I). Our data point to a subgroup of GG with cellular atypia in glial and neuronal cell components, adverse postsurgical outcome, and genetically characterized byPTPN11and other Noonan syndrome-related alterations of theRAS-/MAP-Kinase signaling pathway. These findings need prospective validation in clinical practice as they argue for an adapted WHO grading system in developmental, glio-neuronal tumors associated with early-onset focal epilepsy. These findings also open avenues for targeted medical treatment.