bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiency in
Ever2
does not increase susceptibility of mice to pathogenesis by the mouse papillomavirus, MmuPV1
Authors: Torres Alexandra D. , King Renee E. , Uberoi Aayushi , Buehler Darya , Yoshida Satoshi , Ward-Shaw Ella , Lambert Paul F.
Published: June 2024

Epidermodysplasia verruciformis (EV) is a rare genetic skin disorder that is characterized by the development of papillomavirus-induced skin lesions that can progress to squamous cell carcinoma (SCC). Certain high-risk, cutaneous β-genus human papillomaviruses (β-HPVs), in particular HPV5 and HPV8, are associated with inducing EV in individuals who have a homozygous mutation in one of three genes tied to this disease:
EVER1
,
EVER2
, or
CIB1. EVER1
and
EVER2
are also known as
TMC6
and
TMC8,
respectively. Little is known about the biochemical activities of
EVER
gene products or their roles in facilitating EV in conjunction with β-HPV infection. To investigate the potential effect of
EVER
genes on papillomavirus infection, we pursued
in vivo
infection studies by infecting
Ever2
-null mice with mouse papillomavirus (MmuPV1). MmuPV1 shares characteristics with β-HPVs including similar genome organization, shared molecular activities of their early, E6 and E7, oncoproteins, the lack of a viral E5 gene, and the capacity to cause skin lesions that can progress to SCC. MmuPV1 infections were conducted both in the presence and absence of UVB irradiation, which is known to increase the risk of MmuPV1-induced pathogenesis. Infection with MmuPV1 induced skin lesions in both wild-type and
Ever2
-null mice with and without UVB. Many lesions in both genotypes progressed to malignancy, and the disease severity did not differ between
Ever2
-null and wild-type mice. However, somewhat surprisingly, lesion growth and viral transcription was decreased, and lesion regression was increased in
Ever2
-null mice compared with wild-type mice. These studies demonstrate that
Ever2
-null mice infected with MmuPV1 do not exhibit the same phenotype as human EV patients infected with β-HPVs.

IMPORTANCE

Humans with homozygous mutations in the
EVER2
gene develop epidermodysplasia verruciformis (EV), a disease characterized by predisposition to persistent β-genus human papillomavirus (β-HPV) skin infections, which can progress to skin cancer. To investigate how EVER2 confers protection from papillomaviruses, we infected the skin of homozygous
Ever2
-null mice with mouse papillomavirus MmuPV1. Like in humans with EV, infected
Ever2
-null mice developed skin lesions that could progress to cancer. Unlike in humans with EV, lesions in these
Ever2
-null mice grew more slowly and regressed more frequently than in wild-type mice. MmuPV1 transcription was higher in wild-type mice than in
Ever2
-null mice, indicating that mouse EVER2 does not confer protection from papillomaviruses. These findings suggest that there are functional differences between MmuPV1 and β-HPVs and/or between mouse and human EVER2.
A food color-based colorimetric assay for
Cryptococcus neoformans
laccase activity
Authors: Sanchez Ramirez Lia , Dragotakes Quigly , Casadevall Arturo
Published: June 2024

Cryptococcus neoformans
is a fungal pathogen that causes cryptococcosis primarily in immunocompromised patients, such as those with HIV/AIDS. One survival mechanism of
C. neoformans
during infection is melanin production, which catalyzed by laccase and protects fungal cells against immune attack. Hence, the comparative assessment of laccase activity is useful for characterizing cryptococcal strains. We serendipitously observed that culturing
C. neoformans
with food coloring resulted in degradation of some dyes with phenolic structures. Consequently, we investigated the color changes for the food dyes metabolized by
C. neoformans
laccase and by using this effect explored the development of a colorimetric assay to measure laccase activity. We developed several versions of a food dye-based colorimetric laccase assay that can be used to compare the relative laccase activities between different
C. neoformans
strains. We found that phenolic color degradation was glucose-dependent, which may reflect changes in the reduction properties of the media. Our food color-based colorimetric assay has several advantages, including lower cost, irreversibility, and not requiring constant monitoring , over the commonly used 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay for determining laccase activity. This method has potential applications to bioremediation of water pollutants in addition to its use in determining laccase virulence factor expression.

IMPORTANCE

Cryptococcus neoformans
is present in the environment, and while infection is common, disease occurs mostly in immunocompromised individuals.
C. neoformans
infection in the lungs results in symptoms like pneumonia, and consequently, cryptococcal meningitis occurs if the fungal infection spreads to the brain. The laccase enzyme catalyzes the melanization reaction that serves as a virulence factor for
C. neoformans
. Developing a simple and less costly assay to determine the laccase activity in
C. neoformans
strains can be useful for a variety of procedures ranging from studying the relative virulence of cryptococci to environmental pollution studies.
EasyNAT Malaria: a simple, rapid method to detect
Plasmodium
species using cross-priming amplification technology
Authors: Dong Liu , Xu Qianqian , Shen Linjie , Cao Ruoshui , Deng Xuan , Chen Jian , Jiang Haoqin , Guan Ming
Published: June 2024

Malaria infection remains a serious threat to human health worldwide. Rapid and accurate detection technology is crucial for preventing malaria transmission and minimizing damage. We aimed to establish and validate a new rapid molecular detection method for malaria, called EasyNAT Malaria Assay, targeting
Plasmodium vivax
,
Plasmodium falciparum
,
Plasmodium ovale
, and
Plasmodium malariae
. The analytical performance of EasyNAT Malaria Assay was determined using positive materials. We identified 42 clinical samples as malaria positive and 95 negative samples. Each sample was examined by four methods: light microscopy, rapid diagnostic test, EasyNAT Malaria Assay, and digital PCR. Diagnostic accuracy and clinical performance were evaluated. The limit of detection (LOD)
95%
of EasyNAT Malaria was consistently 40 parasites/mL. It specifically amplified
Plasmodium
and performed with reliable repeatability and reproducibility. In 137 clinical samples, EasyNAT Malaria detected four more positive samples than microscopic examination and two more positive samples than rapid diagnostic test (RDT). One clinical sample was positive only under digital PCR. However, no significant differences statistically in sensitivity or specificity were observed. Compared with microscopy, the total, positive, and negative concordance rates of EasyNAT were 97.08%, 100%, and 95.79%, respectively. Enhanced diagnostic accuracy of EasyNAT Malaria in patients who had taken anti-malarial medication before their clinical appointment was observed. The EasyNAT Malaria Assay has good detection efficiency for clinical samples, presents a promising molecular detection tool in clinical practice, and is particularly suitable for rapid screening of high-risk populations in the emergency room.

IMPORTANCE

This study established and validated EasyNAT Malaria Assay as a promising molecular detection tool for malaria screening of high-risk populations in clinical practice. This novel isothermal amplification method may effectively facilitate the rapid diagnosis of malaria and prevent its transmission.
Risk factors for curable sexually transmitted infections among youth: findings from the STICH population survey in Zimbabwe
Authors: Martin Kevin , Dauya Ethel , Simms Victoria , Bandason Tsitsi , Azizi Steven , Machiha Anna , Shamu Tinei , Musiyandaka Primrose , Mwaturura Tinashe , Francis Suzanna C , Mackworth-Young Constance R S , Busza Joanna , Mavodza Constancia , Tembo Mandi , Hayes Richard J , Kranzer Katharina , Ferrand Rashida A , Dziva Chikwari Chido
Published: June 2024

Objectives

Youth are at high risk of sexually transmitted infections (STIs) in Africa. We aimed to determine the risk factors for curable STIs in youth in Zimbabwe.

Methods

A population-based survey was conducted among randomly selected 18–24 year-olds in 16 communities across two provinces in Zimbabwe to ascertain outcomes for a cluster randomised trial investigating the impact of community-based STI screening for youth on population prevalence of STIs. Participants underwent an interviewer-administered questionnaire, HIV testing and screening forChlamydia trachomatis(CT),Neisseria gonorrhoeae(NG) andTrichomonas vaginalis(TV). Risk factors for curable STIs were explored through multivariable logistic regression.

Results

Of the 5601 participants, 62.5% (n=3500) were female, and the median age was 20 (IQR 19–22) years. HIV prevalence was 6.3% (351/5556), and 55.4% (1939/3501) reported condomless sex at last intercourse. Only 7.2% (401/5599) reported STI symptoms, but CT/NG/TV prevalence was 19.8% (1107/5601). On multivariable analysis, factors associated with STI diagnosis included being aged 21–24 years (adjusted OR (aOR) 1.37, 95% CI 1.17 to 1.61); female sex (aOR 2.11, 95% CI 1.76 to 2.53); being unemployed/informally employed (compared with in education/formal employment) (aOR 1.35, 95% CI 1.13 to 1.61); increasing number of sexual partners in the preceding 12 months (one partner: aOR 2.23, 95% CI 1.73 to 2.88; two partners: aOR 2.39, 95% CI 1.69 to 3.39); living with HIV (aOR 1.44, 95% CI 1.07 to 1.94); and previous attempted suicide (aOR 1.58, 95% CI 1.08 to 2.32).

Conclusions

The prevalence of STIs among youth in Zimbabwe is high, particularly among those with HIV. In addition to moving away from syndromic STI management and strengthening implementation of existing prevention tools, there is a need for a more holistic focus on broader risk factors such as mental health and employment opportunities, and of integration of HIV and STI programming.

Trial registration number

ISRCTN15013425,NCT03719521.
Serratus anterior plane block improves pain and incentive spirometry volumes in trauma patients with multiple rib fractures: a prospective cohort study
Authors: Sadauskas Victor , Fofana Mariame , Brunson Dalton , Choi Jeff , Spain David , Quinn James V , Duanmu Youyou
Published: June 2024

Background

Rib fractures are common injuries associated with considerable morbidity, long-term disability, and mortality. Early, adequate analgesia is important to mitigate complications such as pneumonia and respiratory failure. Regional anesthesia has been proposed for rib fracture pain control due to its superior side effect profile compared with systemic analgesia. Our objective was to evaluate the effect of emergency physician-performed, ultrasound-guided serratus anterior plane block (SAPB) on pain and respiratory function in emergency department patients with multiple acute rib fractures.

Methods

This was a prospective observational cohort study of adult patients at a level 1 trauma center who had two or more acute unilateral rib fractures. Eligible patients received a SAPB if an emergency physician trained in the procedure was available at the time of diagnosis. Primary outcomes were the absolute change in pain scores and percent change in expected incentive spirometry volumes from baseline to 3 hours after rib fracture diagnosis.

Results

38 patients met eligibility criteria, 15 received the SAPB and 23 did not. The SAPB group had a greater decrease in pain scores at 3 hours (−3.7 vs. −0.9; p=0.003) compared with the non-SAPB group. The SAPB group also had an 11% (CI 1.5% to 17%) increase in percent expected spirometry volumes at 3 hours which was significantly better than the non-SAPB group, which had a −3% (CI −9.1% to 2.7%) decrease (p=0.008).

Conclusion

Patients with rib fractures who received SAPB as part of a multimodal pain control strategy had a greater improvement in pain and respiratory function compared with those who did not. Larger trials are indicated to assess the generalizability of these initial findings.
An Empirical Study on the Characteristics of Database Access Bugs in Java Applications
Authors: Liu Wei , Mondal Shouvick , Chen Tse-Hsun (Peter)
Published: June 2024

Database-backed applications rely on the database access code to interact with the underlying database management systems (DBMSs). Although many prior studies aim at database access issues like SQL anti-patterns or SQL code smells, there is a lack of study of database access bugs during the maintenance of database-backed applications. In this paper, we empirically investigate 423 database access bugs collected from seven large-scale Java open-source applications that use relational DBMSs (e.g., MySQL or PostgreSQL). We study the characteristics (e.g., occurrence and root causes) of the bugs by manually examining the bug reports and commit histories. We find that the number of reported database and non-database access bugs share a similar trend but their modified files in bug fixing commits are different. Additionally, we generalize categories of the root causes of database access bugs, containing five main categories (SQL queries, Schema, API, Configuration, and SQL query result) and 25 unique root causes. We find that the bugs pertaining to SQL queries, Schema, and API cover 84.2% of database access bugs across all studied applications. In particular, SQL queries bug (54%) and API bug (38.7%) are the most frequent issues when using JDBC and Hibernate, respectively. Finally, we provide a discussion on the implications of our findings for developers and researchers.
Supplementary Figure S4 from Nucleolar Localization of the RNA Helicase DDX21 Predicts Survival Outcomes in Gynecologic Cancers
Authors: Aljardali Marwa W. , Kremer Kevin M. , Parker Jessica E. , Fleming Elaine , Chen Hao , Lea Jayanthi S. , Kraus W. Lee , Camacho Cristel V.
Published: June 2024

PARP1 and DDX21 are more highly expressed in tumor tissues compared to normal tissues in different cancer types
Supplementary Figure S1 from Nucleolar Localization of the RNA Helicase DDX21 Predicts Survival Outcomes in Gynecologic Cancers
Authors: Aljardali Marwa W. , Kremer Kevin M. , Parker Jessica E. , Fleming Elaine , Chen Hao , Lea Jayanthi S. , Kraus W. Lee , Camacho Cristel V.
Published: June 2024

Endometrial and ovarian cancer cell lines are HR-proficient
FIGURE 1 from Nucleolar Localization of the RNA Helicase DDX21 Predicts Survival Outcomes in Gynecologic Cancers
Authors: Aljardali Marwa W. , Kremer Kevin M. , Parker Jessica E. , Fleming Elaine , Chen Hao , Lea Jayanthi S. , Kraus W. Lee , Camacho Cristel V.
Published: June 2024

Niraparib inhibits ADPRylation and disrupts the nucleolar localization of DDX21 in endometrial and ovarian cancer cells. Inhibition of PARP1 catalytic activity in endometrial cancer cell lines (Ishikawa, HEC-1-A, KLE; A) and ovarian cancer cell lines (OVCAR3, OVCAR4, HCC5012; B) by niraparib promotes the redistribution of DDX21 from the nucleolus to the nucleoplasm but does not affect the nucleolar localization of NOP58 as assayed by immunofluorescent staining. C, Quantification of the results from experiments shown in A and B showing the proportion of cells that have disrupted nucleoplasmic localization of DDX21. Each bar represents the mean + SEM; n = 3 (endometrial), n = 6 (ovarian). Bars marked with asterisks are significantly different; Student t test; *, P < 0.05; **, P < 0.01; ***, P < 0.001. D, ADPRylation (PAR) is inhibited in endometrial and ovarian cancer cells treated with niraparib. PARP1 and DDX21 protein expression levels are not affected by niraparib treatment as assayed by Western blotting. E, Quantification of PAR levels from experiments shown in D for endometrial and ovarian cancer cell lines with and without niraparib treatment. Each bar represents the mean + SEM; n = 3. Bars marked with asterisks are significantly different; Student t test; *, P < 0.05; **, P < 0.01.
Data from Nucleolar Localization of the RNA Helicase DDX21 Predicts Survival Outcomes in Gynecologic Cancers
Authors: Aljardali Marwa W. , Kremer Kevin M. , Parker Jessica E. , Fleming Elaine , Chen Hao , Lea Jayanthi S. , Kraus W. Lee , Camacho Cristel V.
Published: June 2024

Abstract
Cancer cells with DNA repair defects (e.g., BRCA1/2 mutant cells) are vulnerable to PARP inhibitors (PARPi) due to induction of synthetic lethality. However, recent clinical evidence has shown that PARPi can prevent the growth of some cancers irrespective of their BRCA1/2 status, suggesting alternative mechanisms of action. We previously discovered one such mechanism in breast cancer involving DDX21, an RNA helicase that localizes to the nucleoli of cells and is a target of PARP1. We have now extended this observation in endometrial and ovarian cancers and provided links to patient outcomes. When PARP1-mediated ADPRylation of DDX21 is inhibited by niraparib, DDX21 is mislocalized to the nucleoplasm resulting in decreased rDNA transcription, which leads to a reduction in ribosome biogenesis, protein translation, and ultimately endometrial and ovarian cancer cell growth. High PARP1 expression was associated with high nucleolar localization of DDX21 in both cancers. High nucleolar DDX21 negatively correlated with calculated IC50s for niraparib. By studying endometrial cancer patient samples, we were able to show that high DDX21 nucleolar localization was significantly associated with decreased survival. Our study suggests that the use of PARPi as a cancer therapeutic can be expanded to further types of cancers and that DDX21 localization can potentially be used as a prognostic factor and as a biomarker for response to PARPi.
Significance:
Currently, there are no reliable biomarkers for response to PARPi outside of homologous recombination deficiency. Herein we present a unique potential biomarker, with clear functional understanding of the molecular mechanism by which DDX21 nucleolar localization can predict response to PARPi.
A new species of tanager (Aves: Thraupidae) from the Eastern slopes of the Andes
Authors: CAVARZERE VAGNER , COSTA THIAGO VERNASCHI V. , CABANNE GUSTAVO S. , TRUJILLO-ARIAS NATALIA , MARCONDES RAFAEL S. , SILVEIRA LUÍS F.
Published: June 2024

The Black-goggled Tanager (Trichothraupis melanops) is a South American forest species that comprises two disjunct populations in the Atlantic Forest and in the Andes. During visits to natural history museums, we noticed morphological differences between these populations, which led to a taxonomic revision of the species based on plumage patterns and morphometry. Our analyses revealed that both populations are fully diagnosable, and that the Andean population represents an undescribed taxon, which we name Trichothraupis griseonota sp. nov. The new taxon differs from T. melanops by the extension of black in the faces of the males, covering the auricular region, and a greyer shade on the back (instead of olive). A previous mtDNA study with Trichothraupis is consistent with our conclusions that a new taxon requires recognition. The new species is found from 400 m up to 1,700 m on the eastern slopes of the Andes in Peru, Bolivia, and northwestern Argentina, inhabiting Tucumano-Boliviano and Yungas Forests as opposed to the Atlantic Forests where T. melanops is found. The biogeographical disjunction of the two species is similar to what has been observed for other bird species and subspecies, whereby avian lineages are allopatrically distributed and separated by the Chaco-Cerrado vegetation. The description of this taxon reinforces the importance of continued studies and analyses of museum specimens, which may yet reveal little-known patterns and undescribed taxa.
Multiple targets, germline BRCA1 mutation and HRD in a lung cancer patient: Molecular considerations and treatment decision-making
Authors: Perrone Fabiana , Facchinetti Francesco , Pellegrino Benedetta , Minari Roberta , Gnetti Letizia , Azzoni Cinzia , Bottarelli Lorena , Campanini Nicoletta , Grau-Bejar Juan Francisco , Mingozzi Anna , Cognigni Valeria , Tiseo Marcello
Published: June 2024

Introduction:

Several biomarkers are currently available to address targeted treatments in cancer patients, with lung malignancies representing one of the best examples.

Case description:

We report the case of a patient affected by advanced non-small cell lung cancer with an uncommon histology and a complex biology. The use of a large next-generation sequencing (NGS) NGS panel allowed us to identify an extremely rare BRAF mutation (V600Q), a MET amplification, a high tumor mutational burden, a germline pathogenetic BRCA1 mutation and a homologous recombination deficiency through RAD51 assay. The treatment decision was driven by the abundance of molecular information.

Conclusions:

This case highlights that an attentive and critical evaluation of molecular reports is key for the tailoring of treatment algorithms at the patient-level scale.
Sustainability Implications of Working-From-Home (WFH): A Systematic Review of the Travel Behavior Literature
Authors: Halefom Tmnit Hailu , Moglia Magnus , Nygaard Christian (Andi) , Pojani Dorina
Published: June 2024

This systematic literature review investigates whether and how working-from-home (WFH) affects travel behavior in the working population, and then assesses whether the changes, if any, generate environmental, social, or economic benefits. We rely on a final sample of forty-eight peer-reviewed articles, selected following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Throughout the study, we distinguish between the pre-, during, and post-COVID-19 evidence. We find that there are many environmental, social, and economic benefits associated with WFH but attaining them is not straightforward, partly because current urban patterns were not created with WFH in mind and lifestyle adjustments can offset any gains associated with WFH. A decrease in overall travel distance is only accrued when most employees (in jobs that do not require face-to-face contact) work from home three or more times a week.
Childhood Parental Neglect, Abuse and Rejection Among Transgender Women: A Cross-Sectional Study in Rio de Janeiro, Brazil
Authors: Rafael Ricardo de Mattos Russo , Silva Nathalia Leal , Depret Davi Gomes , Gonçalves de Souza Santos Helena , Silva Kleison Pereira da , Catarina Barbachan Moares Advi , Braga do Espírito Santo Tiago , Caravaca-Morera Jaime Alonso , Wilson Erin C. , Moreira Jalil Emilia , Knupp Virginia Maria de Azevedo Oliveira , Veloso Valdiléa Gonçalves , Grinsztejn Beatriz , Velasque Luciane de Souza
Published: June 2024

We aimed to estimate the proportions of childhood parental neglect, abuse, and rejection and to evaluate the co-occurrence of these experiences among transgender women in Rio de Janeiro, Brazil. This was a cross-sectional study with a convenience sample enrolled between July 2019 and March 2020, using an adapted version of the Childhood Trauma Questionnaire. Proportions and corresponding confidence intervals (CI) were calculated. Kendall correlation with Tau-b estimator was used in the bivariate analyses. We gathered data from 139 participants. The most prevalent types of childhood traumas were emotional abuse (60.43%, 95% CI [51.79, 68.62]), physical abuse (57.55%, 95% CI [48.90, 65.89]) and sexual abuse (44.60%, 95% CI [36.18, 53.27]). Severe to extreme physical and emotional abuse occurred among 40.29% (95% CI [32.06, 48.93]) and 5.75% (95% CI [2.51, 11.02]) of participants, respectively. The proportion of parental rejection (eviction) was 32.37% (95% CI [25.04, 40.69]) and occurred with the other forms of abuse, except sexual abuse. Multiple types of childhood abuse, neglect, and parental rejection were observed among transgender women in our sample. The harmful effects of childhood abuse on the mental and physical health of people in the transgender population are of concern, particularly considering the cumulative effect produced by the co-occurrence of such events and their harmful lifetime effects. It is urgently necessary to debate and formulate public policies to ensure the right to gender expression from childhood.
Who reads Renan
Authors: Steedman Carolyn
Published: June 2024

This article claims Virginia Woolf as a historian of the period 1880–1937 in Britain. In her 1937 novel The Years, Woolf employed the religious and cultural history of Ernest Renan, most likely his Vie de Jésus (1863), to produce her own. By unravelling what Renan wrote, what Woolf read and wrote, and what Renan meant, in his own terms and to a contemporary British audience, we can begin to consider the role of religious criticism in the making of historical and literary modernity.
The Construction of Interpersonal Meanings in Jiaqi Li's E-Commerce Live Streams: Integrating Verbal and Visual Semiotics
Authors: Zhang Huiyu , Hou Yining
Published: June 2024

This study conducts a multimodal discourse analysis of the live streaming of Jiaqi Li, a well-known Chinese streamer. Integrating systemic functional grammar and systemic visual grammar to explore the construction of interpersonal meanings in Li's live streams, the authors found that Li uses verbal semiotics to convey information and feelings and, more important, to create his different interactive roles as an authoritative opinion leader, a protector of consumers’ benefits, and a friend who shares his experiences and recommends products. This study offers insight into e-commerce discourse and communication, adding to the literature on live streaming in commerce and business communication.
Single-Cell Molecular Profiling of Head and Neck Squamous Cell Carcinoma Reveals Five Dysregulated Signaling Pathways Associated With Circulating Tumor Cells
Authors: Stucky Andres , Viet Chi T. , Aouizerat Bradley E. , Ye Yi , Doan Coleen , Mundluru Tarun , Sedhiazadeh Parish , Sinha Uttam K. , Chen Xuelian , Zhang Xi , Li Shengwen Calvin , Cai Jin , Zhong Jiang F.
Published: June 2024

Objectives

To determine the dysregulated signaling pathways of head and neck squamous cell carcinoma associated with circulating tumor cells (CTCs) via single-cell molecular characterization.

Introduction

Head and neck squamous cell carcinoma (HNSCC) has a significant global burden and is a disease with poor survival. Despite trials exploring new treatment modalities to improve disease control rates, the 5 year survival rate remains low at only 60%. Most cancer malignancies are reported to progress to a fatal phase due to the metastatic activity derived from treatment-resistant cancer cells, regarded as one of the most significant obstacles to develope effective cancer treatment options. However, the molecular profiles of cancer cells have not been thoroughly studied.

Methods

Here, we examined in-situ HNSCC tumors and pairwisely followed up with the downstream circulating tumor cells (CTCs)-based on the surrogate biomarkers to detect metastasis that is established in other cancers – not yet being fully adopted in HNSCC treatment algorithms.

Results

Specifically, we revealed metastatic HNSCC patients have complex CTCs that could be defined through gene expression and mutational gene profiling derived from completed single-cell RNASeq (scRNASeq) that served to confirm molecular pathways inherent in these CTCs. To enhance the reliability of our findings, we cross-validated those molecular profiles with results from previously published studies.

Conclusion

Thus, we identified 5 dysregulated signaling pathways in CTCs to derive HNSCC biomarker panels for screening HNSCC in situ tumors.
Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment
Authors: Gervaso Lorenzo , Ciardiello Davide , Gregato Giuliana , Guidi Lorenzo , Valenza Carmine , Ascione Liliana , Boldrini Laura , Frassoni Samuele , Cella Chiara Alessandra , Spada Francesca , Funicelli Luigi , De Roberto Giuseppe , Petz Wanda , Borin Simona , Gerardi Marianna Alessandra , Bottiglieri Luca , Tamayo Darina , Bertani Emilio , Fumagalli Romario Uberto , Bagnardi Vincenzo , Curigliano Giuseppe , Bertolini Francesco , Fazio Nicola , Zampino Maria Giulia
Published: June 2024

Background:

The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy.

Objectives:

We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes.

Design:

Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery.

Methods:

Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS).

Results:

Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10–1.26), p = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02–1.07), p = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63–8.36, p = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35–4.06, p = 0.79).

Conclusion:

Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.
Adjuvant donafenib for hepatocellular carcinoma patients at high-risk of recurrence after radical resection: a real-world experience
Authors: Zhang Shenyu , Yang Guibin , Song Ruipeng , Wang Wei , Meng Fanzheng , Yin Dalong , Wang Jiabei , Zhang Shugeng , Cai Wei , Liu Yao , Luo Dayong , Wang Jizhou , Liu Lianxin
Published: June 2024

Background:

Adjuvant therapy is used to reduce the risk of hepatocellular carcinoma (HCC) recurrence and improve patient prognosis. Exploration of treatment strategies that are both efficacious and safe has been extensively performed in the recent years. Although donafenib has demonstrated good efficacy in the treatment of advanced HCC, its use as adjuvant therapy in HCC has not been reported.

Objectives:

To investigate the efficacy and safety of postoperative adjuvant donafenib treatment in patients with HCC at high-risk of recurrence.

Design:

Retrospective study.

Methods:

A total of 196 patients with HCC at high-risk of recurrence were included in this study. Of these, 49 received adjuvant donafenib treatment, while 147 did not. Survival outcomes and incidence of adverse events (AEs) in the donafenib-treated group were compared. Inverse probability of treatment weighting (IPTW) method was used.

Results:

The median follow-up duration was 21.8 months [interquartile range (IQR) 17.2–27.1]. Before IPTW, the donafenib-treated group exhibited a significantly higher 1-year recurrence-free survival (RFS) rate (83.7% versus 66.7%, p = 0.023) than the control group. Contrarily, no significant difference was observed in the 1-year overall survival (OS) rates between the two groups (97.8% versus 91.8%, p = 0.120). After IPTW, the 1-year RFS and OS rates (86.6% versus 64.8%, p = 0.004; 97.9% versus 89.5%, p = 0.043, respectively) were higher than those in the control group. Multivariate analysis revealed that postoperative adjuvant donafenib treatment was an independent protective factor for RFS. The median duration of adjuvant donafenib treatment was 13.6 (IQR, 10.7–18.1) months, with 44 patients (89.8%) experienced AEs, primarily grade 1–2 AEs.

Conclusion:

Postoperative adjuvant donafenib treatment effectively reduced early recurrence among patients with HCC at high-risk of recurrence, while exhibiting favorable safety and tolerability profile. However, these findings warrant further investigation.
Updates of primary central nervous system lymphoma
Authors: Wu Jiaying , Zhou Delian , Zhu Xiaojian , Zhang Yicheng , Xiao Yi
Published: June 2024

Lymphoma occurring in the central nervous system is considered primary central nervous system lymphoma (PCNSL), usually without systematic lesions. Over the last few decades, a deep understanding of PCNSL has been lacking due to the low incidence rate, and the overall survival and progression-free survival of patients with PCNSL are lower than those with other types of non-Hodgkin lymphoma. Recently, there have been several advancements in research on PCNSL. Advances in diagnosis of the disease are primarily reflected in the promising diagnostic efficiency of novel biomarkers. Pathogenesis mainly involves abnormal activation of nuclear factor kappa-B signaling pathways, copy number variations, and DNA methylation. Novel therapies such as Bruton’s tyrosine kinase inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, and phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors are being evaluated as possible treatment options for PCNSL, especially for relapsed/refractory (R/R) cases. Several clinical trials also indicated the promising feasibility and efficacy of chimeric antigen receptor T-cell therapy for selected R/R PCNSL patients. This review focuses on discussing recent updates, including the diagnosis, pathogenesis, and novel therapy of PCNSL.
Effects of virtual distant viewing technology on preventing nearwork-induced ocular parameter changes
Authors: Yi Zhen , Ningli Wang , Kai Cao , Yan Huang , Wei Zhang
Published: June 2024

Purpose

This study investigates whether virtual distant viewing technology can prevent nearwork-induced ocular parameter changes.

Methods

Twenty-six volunteers read a textbook on one day and the same content on a virtual distant viewing display on another day based on a randomization sequence, with both reading sessions at 33 cm for 4 hours. Visual acuity, diopter, ocular biology, visual fatigue, and accommodative function before and after the nearwork, as well as the number of pages read, were recorded.

Results

After 4 hours of nearwork in the textbook group, the spherical equivalent refraction decreased from −3.13 ± 2.65 D to −3.32 ± 2.70 D ( P < 0.001), corneal thickness decreased from 531.6 ± 33.5 μm to 528.9 ± 33.0 μm ( P = 0.015), anterior chamber depth decreased from 3.65 ± 0.35 mm to 3.60 ± 0.30 mm ( P = 0.002), accommodative facility increased from 15.1 ± 3.5 to 16.4 ± 3.9 ( P = 0.018), and subjective visual fatigue increased from 14.0 ± 9.2 to 19.3 ± 7.6 ( P = 0.002); no significant changes were seen in the other parameters. In the virtual distant viewing group, the spherical equivalent refraction (from −3.17 ± 2.60 D to −3.11 ± 2.73 D, P = 0.427), corneal thickness (from 531.9 ± 32.8 μm to 529.7 ± 33.2 μm, P = 0.054), and anterior chamber depth (from 3.67 ± 0.35 mm to 3.69 ± 0.32 mm, P = 0.331) did not show significant changes, whereas accommodative facility increased from 14.7 ± 5.8 to 15.9 ± 5.5 ( P = 0.042) and subjective visual fatigue increased from 13.5 ± 8.4 to 18.9 ± 8.6 ( P = 0.002). In addition, choroidal thickness (from 217.7 ± 76.0 μm to 243.0 ± 85.0 μm, P = 0.043), positive relative accommodation (from −2.32 ± 1.07 D to −2.85 ± 0.89 D, P = 0.007), and amplitude of accommodation (from 7.26 ± 1.41 D to 7.89 ± 1.69 D, P = 0.022) also significantly increased in the virtual distant viewing group. The textbook group and the virtual distant viewing group read 176.0 ± 133.1 pages and 188.0 ± 102.0 pages, respectively, and there was no significant difference between the two groups ( P = 0.708).

Conclusion

Virtual distant viewing technology can prevent the increase in myopia degree due to nearwork and improve accommodation function without increasing visual fatigue.
A Rapid Review of Designing a Code of Practice for the Music Industry and Mental Health
Authors: Jepson Rachel , Sims Michael , Ravalier Jermaine
Published: June 2024

The contemporary music industry is composed of numerous therapeutic resources, small-scale interventions, technological solutions, triage services, and more. The aim of this rapid review is to identify the mental health issues that members of the music industry may experience, and what will inform the development of a music industry “code of practice” for mental health. Research undertaken internationally within the music industry since the 2016 “Can Music Make You Sick?” study has identified that members of the UK music industry community experience negative mental health symptoms notably more than other industries. Negative mental health symptoms within this review can be defined as panic attacks and/or high levels of anxiety and/or depression. A code of practice is a set of written regulations issued by a professional association or an official body that explains how people working in a particular profession should behave. A code of practice helps workers in a particular profession to comply with ethical and health standards. A code of practice within the contemporary music industry would provide a framework within which music industry members can work. Music industry members are defined herein as anyone involved in and/or working in the music industry. It is important to make this clarification, as many of the studies around mental health in the music industry focus on musicians, whereas all roles in the music industry have the potential to struggle with their mental health. The literature identified fundamental problems relating to mental health and the music industry. Help Musicians’ “Can Music Make You Sick?” study from 2016 found that from over 2,000 respondents, 69% of musicians suffered from depression. In Canada, a small study of 50 respondents found that 20% disclosed suicidal thoughts.
A Systematic Review and Content Analysis of School Counseling Mental Health Supports for Black Youth: Implications for Research and Practice
Authors: Lopez-Perry Caroline , Mora Liliana , Placeres Vanessa , Robertson Adrianne
Published: June 2024

The study conducted a 10-year (2011–2021) content analysis of K–12 Black student mental health literature. The analysis aimed to review school counseling literature concerning mental health support for Black youth. Findings revealed that the majority of the qualifying studies had Black students as the sample focus, and most frequently examined prevention services and protective factors for poor mental health. We address research gaps and provide future research and practice recommendations.
The Development of New Scoring System to Define the Presence of Instability and the Need of Fusion in Degenerative Lumbar Spinal Stenosis - Jakarta Instability Score
Authors: Saleh Ifran , Hutami Witantra Dhamar , Librianto Didik , Prasetyo Marcel , Rahyussalim Ahmad Jabir , Hendriarto Andra , Noor Erwin Ardian , Rifki Aliyya
Published: June 2024

Study Design

Systematic review, expert opinion and Delphi technique, and validity and reliability studies.

Objective

We developed Jakarta Instability Score (JIS) to identify spinal instability and the need of fusion in degenerative lumbar spinal stenosis (LSS).

Methods

This study consisted of systematic review to find predictors of spinal instability, expert opinion and modified Delphi technique to develop JIS, and validity and reliability studies of the newly developed JIS.

Results

A total of 54 studies were included in the systematic reviews to obtain predictors of spinal instability. Through expert opinion and modified Delphi technique, JIS was developed and consisted of the clinical component (back pain), dynamic radiograph component (dynamic translation and angulation), and MRI component (facet joint effusion), each of the component would be scored, and the total scoring would be from 0 to 14. The final scoring would classify patients into three groups: stable group (score of 0 to 4) in which the fusion is not needed, potentially unstable group (score of 5 to 8) in which the decision of fusion is based on surgeon’s clinical judgment, and unstable group (score of 9 to 14) in which the fusion is needed. Final step of study concluded that this JIS had a high validity and reliability.

Conclusion

The newly developed JIS was a valid and reliable scoring system that could help to identify the presence of instability in LSS and can be used as a guideline to decide whether spinal fusion will be needed.
Optimizing biochar, vermicompost, and duckweed amendments to mitigate arsenic uptake and accumulation in rice (Oryza sativa L.) cultivated on arsenic-contaminated soil
Authors: Roy Rana , Hossain Akram , Sharif Md. Omar , Das Mitali , Sarker Tanwne
Published: June 2024

The accumulation of arsenic (As) in rice (Oryza sativa L.) grain poses a significant health concern in Bangladesh. To address this, we investigated the efficacy of various organic amendments and phytoremediation techniques in reducing As buildup in O. sativa. We evaluated the impact of five doses of biochar (BC; BC0.1: 0.1%, BC0.28: 0.28%, BC0.55: 0.55%, BC0.82: 0.82% and BC1.0: 1.0%, w/w), vermicompost (VC; VC1.0: 1.0%, VC1.8: 1.8%, VC3.0: 3.0%, VC4.2: 4.2% and VC5.0: 5.0%, w/w), and floating duckweed (DW; DW100: 100, DW160: 160, DW250: 250, DW340: 340 and DW400: 400 g m− 2) on O. sativa cultivated in As-contaminated soil. Employing a three-factor five-level central composite design and response surface methodology (RSM), we optimized the application rates of BC-VC-DW. Our findings revealed that As contamination in the soil negatively impacted O. sativa growth. However, the addition of BC, VC, and DW significantly enhanced plant morphological parameters, SPAD value, and grain yield per pot. Notably, a combination of moderate BC-DW and high VC (BC0.55VC5DW250) increased grain yield by 44.4% compared to the control (BC0VC0DW0). As contamination increased root, straw, and grain As levels, and oxidative stress in O. sativa leaves. However, treatment BC0.82VC4.2DW340 significantly reduced grain As (G-As) by 56%, leaf hydrogen peroxide by 71%, and malondialdehyde by 50% compared to the control. Lower doses of BC-VC-DW (BC0.28VC1.8DW160) increased antioxidant enzyme activities, while moderate to high doses resulted in a decline in these activities. Bioconcentration and translocation factors below 1 indicated limited As uptake and translocation in plant tissues. Through RSM optimization, we determined that optimal doses of BC (0.76%), VC (4.62%), and DW (290.0 g m− 2) could maximize grain yield (32.96 g pot− 1, 44% higher than control) and minimize G-As content (0.189 mg kg− 1, 54% lower than control). These findings underscore effective strategies for enhancing yield and reducing As accumulation in grains from contaminated areas, thereby ensuring agricultural productivity, human health, and long-term sustainability. Overall, our study contributes to safer food production and improved public health in As-affected regions.
Comparison of anaesthesia strategies on postoperative nausea and vomiting in laparoscopic sleeve gastrectomy: a randomised controlled trial
Authors: Yang Ying , Liao Bucheng , Deng Ruoxi , Ren Liwei , Sun Yongjie , Xiong Shaowei , Wu Xinhai
Published: June 2024

Background

Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single intervention may not effectively reduce postoperative nausea and vomiting in such patients. This study assessed the effect of an optimised anaesthetic protocol versus a conventional one on postoperative nausea and vomiting in patients who underwent laparoscopic sleeve gastrectomy.

Methods

A single-centre randomised trial was conducted at Peking University Shenzhen Hospital from June 2021 to December 2022. Among 168 patients who underwent laparoscopic sleeve gastrectomy, 116 qualified, and 103 completed the study with available data. Patients were categorized into the conventional group (received sevoflurane and standard fluids) and the optimised group (underwent propofol-based anaesthesia and was administered goal-directed fluids). The primary endpoints were postoperative nausea and vomiting incidence and severity within 24 h.

Results

Postoperative nausea and vomiting assessment at 0–3 h post-surgery revealed no significant differences between groups. However, at 3–24 h, the optimised anaesthetic protocol group showed lower postoperative nausea and vomiting incidence and severity than those of the conventional group (P = 0.005). In the conventional group, 20 (37.04%) patients experienced moderate-to-severe postoperative nausea and vomiting, compared to six (12.25%) patients in the optimised group (odds ratio = 0.237; 95% CI = 0.086, 0.656; P = 0.006). No significant differences were noted in antiemetic treatment, moderate-to-severe pain incidence, anaesthesia recovery, post-anaesthetic care unit stay, or postoperative duration between the groups. While the total intra-operative infusion volumes were comparable, the optimised group had a significantly higher colloidal infusion volume (500 mL vs. 0 mL, P = 0.014) than that of the conventional group.

Conclusions

The incidence and severity of postoperative nausea and vomiting 3–24 h postoperatively in patients who underwent laparoscopic sleeve gastrectomy were significantly lower with propofol-based total intravenous anaesthesia and goal-directed fluid therapy than with sevoflurane anaesthesia and traditional fluid management. Total intravenous anaesthesia is an effective multimodal antiemetic strategy for bariatric surgery.

Trial registration

This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC- 2,100,046,534, registration date: 21 May 2021).