bluuebunny/crossref_metadata_2025 huggingface dataset:
Relaxing radial retinal incisions for the treatment of persistent macular holes
Authors: Camenzind-Zuche Hanna , Janeschitz-Kriegl Lucas , Hasler Pascal , Prünte Christian
Published: September 2023

Purpose

Various surgical techniques have been described for managing persistent macular holes after an unsuccessful vitrectomy with internal limiting membrane (ILM) peeling. However, the closure and functional improvement rates after these procedures are limited. Therefore, the aim of this study was to evaluate the usefulness of radial retinal incisions (retinotomies) in eyes with persistent large macula holes despite previous vitrectomy with ILM peeling.

Design

In a retrospective case series, closure rate and best-corrected visual acuity (BCVA) were evaluated in eyes with persistent macular holes after an unsuccessful vitrectomy that included posterior vitreous detachment and ILM peeling.

Subjects

22 eyes of 22 patients (10 men and 12 women) underwent re-vitrectomy with radial retinal incisions. All the patients had undergone an unsuccessful surgery before.

Methods

Small-incision re-vitrectomy with radial retinal incisions (retinotomies) and air tamponade was performed.

Main Outcome Measurements

For all eyes, high-definition SD-OCT scans (SD-OCT Spectralis, Heidelberg Engineering GmbH, Germany) of the macula were routinely performed before surgery; 1 week and 1 month after surgery; and at final follow-up. Additionally, age, gender, axial length, macular hole diameter, biomicroscopic fundus evaluation and best-corrected visual acuity (BCVA) in logMAR and Snellen at baseline, 1 and 4 months after operation, and at the final follow-up visit were analyzed.

Results

The mean baseline macular hole diameter was 668.5 ± 226.8 μm. At the final examination, 16 (72.72%) of the 22 macula holes were closed. Visual acuity increased in 17 eyes, was stable in 3 eyes, and decreased in 2 eyes owing to central retinal atrophy in both. The mean BCVA increased from logMAR 1.04 ± 0.29 at baseline to 0.57 ± 0.31 (Snellen 0.11 ± 0.05 to 0.33 ± 0.18). In all successful cases, macula hole closure was attained after 3 days, and none of the eyes showed macula hole recurrence.

Conclusion

The results of this limited case series suggest that radial retinal incisions of the rim in persistent macula holes after initial surgery with ILM peeling increase the success rate of macula hole closure and results in a relevant increase in BCVA. However, as the number of eyes included in this series is limited, the results must be confirmed in a study with a larger sample size.
Balancing short-term gains and long-term success in lodging: The role of customer satisfaction and price in hotel profitability model
Authors: Demydyuk Ganna V , Carlbäck Mats
Published: September 2023

This study examines the relationship between revenue and profit drivers and long-term financial performance in the hotel industry based on 17-years data (2004–2020) of six US hotel chains. The analysis creates, tests, and analyzes a cross-level model that examines the complex endogenous relationships, underlying long-term financial performance of hotels. Specifically, we examine the interaction of room price (ADR) and customer satisfaction (ACSI) within a sales-volume-driver framework that impacts financial performance through profitability, measured at both the operating and accounting levels. This study seeks to advance our understanding of these relationships, their characteristics, and their implications for long-term financial performance in the hotel industry. The findings reveal that customer satisfaction is more important than price in achieving long-term financial success in the hotel industry, whereas room nights sold is significant positive driver of all performance levels.
A Quality Improvement Project to Gain Insight Into What Helps Cancer Patients Cope During Outpatient Radiation Therapy Treatments
Authors: Mitchell Chelsy , Simmonds Andrea M. , Stewart Nicholas S.
Published: September 2023

Psychosocial support in cancer care has not been researched or published to the degree of physical support. This type of support includes the mental, emotional, social, and spiritual needs of patients and loved ones. This quality improvement project provides insight for those seeking understanding of what exactly helps cancer patients cope during outpatient radiation therapy treatments. The purpose of this project was to learn what practices benefit patient's coping during outpatient external radiation therapy treatments in order to increase attention given to psychosocial support of future cancer patients receiving outpatient external radiation therapy treatments. Insight from this project was used to create a resource handout for Novant Health Cancer Institute to help increase awareness, discussion, and attention to supporting outpatient radiation therapy patients emotionally and spiritually.
Rethinking the Triple-Nexus: Integrating Peacebuilding and Resilience Initiatives in Conflict Contexts
Authors: Norman Julie M. , Mikhael Drew
Published: September 2023

The triple-nexus was introduced as a conceptual framework to link humanitarian aid, international development, and peace initiatives. However, the peace component was largely undefined, and there was little consideration as to how these components might be integrated within programs. In this article, we revisit the nexus with a focus on how the peace component can best be integrated with resilience programs in conflict contexts. Specifically, we draw from qualitative fieldwork in Burundi, the Democratic Republic of the Congo, Myanmar, and South Sudan, to analyze how local communities are using integrative peace/conflict approaches to enhance resilience in contexts with ongoing violence. We develop a typology of peace/conflict approaches, identify challenges to peacebuilding within the framework, and propose locally led processes for rethinking the nexus for protracted conflicts. We maintain that a hyper-local approach to community problem-solving is where the peace component of the triple-nexus can be most effective in fragile contexts.
Conventional anatomical landmark versus preprocedural ultrasound for thoracic epidural analgesia: A systematic review and meta-analysis
Authors: Sharapi Mahfouz , Mahfouz Amany , Philip Kerollos , Mektebi Ammar , Albakri Khaled
Published: September 2023

Background:

Thoracic epidural analgesia is the gold standard for major thoracic and abdominal surgeries.

Aim:

Ultrasound-guided and landmark-based thoracic epidural insertion are compared in this systematic review.

Methods:

Randomised controlled trials were sought in six databases for a systematic review and meta-analysis. With a 95% confidence interval, a fixed-effects model calculated risk ratio or mean difference. Cochrane risk of bias assessed bias. Four randomised controlled trials were examined.

Findings:

Preprocedural ultrasound increased thoracic epidural placement first-puncture success rate (risk ratio = 1.28, 95% confidence interval (1.05 to 1.56), p value = 0.02) and decreased the need for two or more skin punctures (mean difference = −2.41, 95% confidence interval (−3.34 to −1.47), p value = 0.00001). The ultrasound group reduced needle redirections (risk ratio = 0.6, 95% confidence interval (0.38 to 0.94), p value = 0.02). The epidural block success rate was equal in both groups (risk ratio = 1.02, 95% confidence interval (0.96 to 1.07), p value = 0.6).

Conclusion:

Thoracic epidural insertion is improved by ultrasound but not the success rate. Quality research with larger samples is needed to emphasise these conclusions.
Pursuit or discontinuation of anti-PD1 after 2 years of treatment in long-term responder patients with non-small cell lung cancer
Authors: Ardin Camille , Humez Sarah , Leroy Vincent , Ampere Alexandre , Bordier Soraya , Escande Fabienne , Turlotte Amélie , Stoven Luc , Nunes David , Cortot Alexis , Gauvain Clément
Published: September 2023

Background:

The optimal duration of immune checkpoint inhibitor (ICI) treatment for patients with advanced non-small cell lung cancer (NSCLC) remains to be determined. Treatment durations in cornerstone phase 3 clinical trials vary between a fixed 2-year duration and pursuit until disease progression. Clinical practices may thus differ according to the attending physician.

Objectives:

Here we provide real-world data about treatment decisions at 2 years, with subsequent clinical outcomes.

Design and Methods:

This multicentric observational study included patients with advanced NSCLC whose disease was controlled after 2 years of pembrolizumab or nivolumab. The primary outcome was the decision to discontinue ICI treatment or not, along with factors motivating this decision. Secondary outcomes included progression-free survival (PFS) (according to treatment continuation or not) and adverse events.

Results:

A total of 91 patients were included, of which 60 (66%) had been pre-treated. The programmed death-ligand 1 expression level was ⩾50% in 43 patients (47%). In 61 patients (67%), ICI was continued after 2 years of treatment. This decision was significantly associated with the care center ( p < 0.001) but neither with the tumor response at 2 years, as evaluated by CT scan or PET scan, nor with clinical status, immune-related adverse events, or previous locally treated oligo-progressive disease under ICI. Two years after the 2-year decision, PFS was 68.5%, [95% confidence interval (CI) (53.3–88.0)] in the ‘ICI discontinuation’ group and 64.1% [95% CI (51.9–79.2)] in the ‘ICI pursuit’ group; hazard ratio for relapse was 1.14 [95% CI (0.54–2.30), p = 0.77]. The overall survival rate at 24 months after discontinuation was 89.2% [95% CI (78.4–100)] for the ‘discontinuation’ group and 93.1% [95% CI (85.8–100)] for the ‘pursuit’ group. Given insufficient power, overall survival could not be compared.

Conclusion:

The decision to continue ICI or not after 2 years of treatment depends mainly on the care center and does not seem to impact survival. Larger, randomized data sets are required to confirm this result.
Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis
Authors: Matsumoto Hiromi , Somekawa Kohei , Horita Nobuyuki , Ueda Suguru , Kaneko Megumi , Kaneko Ayami , Fukuda Nobuhiko , Izawa Ami , Kamimaki Chisato , Tanaka Katsushi , Murohashi Kota , Fuji Hiroaki , Tagami Yoichi , Aoki Ayako , Watanabe Keisuke , Hara Yu , Kobayashi Nobuaki , Kaneko Takeshi
Published: September 2023

Background:

Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs).

Objective:

We aimed to assess the frequency of AEs associated with DT.

Design:

This study type is a systematic review and meta-analysis.

Data Sources and Methods:

Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751).

Results:

Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9–87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2–34.4); serious AEs, 34.9% (95% CI: 28.1–41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3–17.4); treatment-related deaths, 0.98% (95% CI: 0.5–1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8–36.3); diarrhea, 21.7% (95% CI: 17.8–25.6); pruritus 17.9% (95% CI: 14.4–21.3); decreased appetite, 17.7% (95% CI: 13.7–22.0); nausea, 15.6% (95% CI: 12.1–19.6). There were no significant differences in these pooled frequencies between subgroups.

Conclusions:

The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy.
Pollution Haven Hypothesis and the Bilateral Trade Between India and China
Authors: Bhat Varadurga , Tantri Malini L.
Published: September 2023

The pollution haven hypothesis is studied from a bilateral trade perspective in this study, taking the reference of two Asian giants, namely, India and China. For this purpose, trade in pollution-intensive industries is analysed using data collected from the United Nations Comtrade dataset based on Standard Industrial Trade Classification codes for 1992–2019. The analysis helps us argue that between the two, China's demand is more pollution-intensive and India is the major supplier of pollution-intensive products. From an environmental perspective, this implies that China seems to be gaining from trade, and India is becoming a pollution haven in its trade with China.
Impact of local drug delivery and natural agents as new target strategies against periodontitis: new challenges for personalized therapeutic approach
Authors: Viglianisi Gaia , Santonocito Simona , Lupi Saturnino Marco , Amato Mariacristina , Spagnuolo Gianrico , Pesce Paolo , Isola Gaetano
Published: September 2023

Periodontitis is a persistent inflammation of the soft tissue around the teeth that affects 60% of the population in the globe. The self-maintenance of the inflammatory process can cause periodontal damage from the alveolar bone resorption to tooth loss in order to contrast the effects of periodontitis, the main therapy used is scaling and root planing (SRP). At the same time, studying the physiopathology of periodontitis has shown the possibility of using a local drug delivery system as an adjunctive therapy. Using local drug delivery devices in conjunction with SRP therapy for periodontitis is a potential tool since it increases drug efficacy and minimizes negative effects by managing drug release. This review emphasized how the use of local drug delivery agents and natural agents could be promising adjuvants for the treatment of periodontitis patients affected or not by cardiovascular disease, diabetes, and other system problems. Moreover, the review evidences the current issues and new ideas that can inspire potential later study for both basic research and clinical practice for a tailored approach.
Third-line treatment patterns and clinical outcomes for metastatic colorectal cancer: a retrospective real-world study
Authors: Deng Ting , Duan Jingjing , Bai Ming , Zhang Le , Li Hongli , Liu Rui , Ning Tao , Ge Shaohua , Wang Xia , Yang Yuchong , Ji Zhi , Wang Feixue , Ba Yi
Published: September 2023

Background:

There are multiple recommendations on the third-line therapy of metastatic colorectal cancer (mCRC); however, no consensus has been reached.

Objectives:

This study aimed to explore the patient demographics and the real-world third-line treatment landscape of mCRC.

Design:

A retrospective real-world cohort study.

Methods:

Electronic medical records of mCRC patients from Tianjin Medical University Cancer Institute and Hospital between 2013 and 2020 were collected. Upon descriptive, comparative, and survival analyses, a retrospective study was conducted to describe demographics and clinical outcomes of mCRC patients receiving third-line treatment.

Results:

Among 218 mCRC patients receiving third-line therapy, 65.5% received chemotherapy combined with or without targeted drugs, followed by anti-angiogenic monotherapy (18.4%), anti-epidermal growth factor receptor drugs (6.9%) and immunotherapy (6.4%). The overall response rate and disease control rate reached 10.2% and 59.2%, respectively; and median progression-free survival (PFS) and overall survival were 4.0 m and 10.7 m, respectively. After Cox multivariate analysis, we found that therapeutic regime was an independent prognostic factor. Compared to patients receiving anti-angiogenic monotherapy, those receiving chemotherapy combined with or without targeted drugs exhibited better prognosis. For patients whose PFS were longer in the front-line treatment, the PFS of third-line therapy was also relatively longer ( p = 0.023). Multiple types of therapies (>3, p = 0.002) or multiple drugs (>5, p = 0.024) in the whole-course management of mCRC are indicators of longer survival.

Conclusion:

Chemotherapy combined with or without targeted therapy remained dominated third-line choice and showed favorable efficacy compared with anti-angiogenic monotherapy. With the application of more types and quantities of effective drugs, patients would achieve better survival.
How politicians learn about public opinion
Authors: Walgrave Stefaan , Soontjens Karolin
Published: September 2023

Politicians learning about public opinion and responding to their resulting perceptions is one key way via which responsive policy-making comes about. Despite the strong normative importance of politicians’ understanding of public opinion, empirical evidence on how politicians learn about these opinions in the first place is scant. Drawing on survey data collected from almost 900 incumbent politicians in five countries, this study presents unique descriptive evidence on which public opinion sources politicians deem most useful. The findings show that politicians deem direct citizen contact and information from traditional news media as the most useful sources of public opinion information, while social media cues and polls are considered much less useful. These findings matter for substantive representation, and for citizens’ feeling of being represented.
Is sexual misconduct training sufficient in the UK's medical schools: Results of a cross-sectional survey and opportunities for improvement
Authors: Dowling Tia , Steele Sarah
Published: September 2023

Sexual misconduct adversely affects the mental and physical health of millions of people each year and has been declared a global pandemic. Incidence in both educational and clinical settings remains high. In the last 5 years, the NHS spent over £4 million settling sexual misconduct-related claims. Effective prevention requires training across all stages of career, beginning in clinical school. Here, we explore training in the UK's medical schools to identify provision and areas for improvement.

Freedom of Information Act 2000 requests for data on training delivery and curricula content.

34 public UK universities offering medical education

not applicable

Provision and delivery of training, mode of delivery, theme, and continuation of training.

All 34 universities responded. Twenty-two identified offering training. Seventeen made it compulsory. A review of curricula identified, however, only 18 did more just than mentioned sexual misconduct. Nine offered training more than once. Twelve did not offer training, of which three identified no plans to offer such training in the future. The most common delivery modes for training were workshops and lectures. The training was most often within the sexual health curriculum, disconnecting it from professionalism.

There is no standardisation of sexual harassment training across the UK's public medical schools. Many future doctors will not have received relevant education when they assume posts in the NHS. Considering the magnitude of this issue and its critical connection to professionalism and collegiality, universities and professional bodies urgently should address this deficiency.
Behavioral Intention to Use Online for Shopping in Bangladesh: A Technology Acceptance Model Analysis
Authors: Islam Shafiqul , Islam Mohammad Fakhrul , Zannat Noor-E-
Published: September 2023

Consumer behavior and the way businesses conduct their operations have changed due to the widespread usage of internet purchasing worldwide. Bangladesh’s reliance on online shopping presents both opportunities and difficulties. The relatively large marketplace is driving up demand for online shopping. On the contrary, the need for greater technological proficiency that underpins online purchasing presents a significant challenge for entrepreneurs, managers, and consumers. This paper employed TAM (Technology Acceptance Model) to explore and predict Bangladeshi customers’ online purchasing intentions. The data were collected from 322 online consumers in Dhaka and analyzed with SEM utilizing SMART PLS 3. The data analysis demonstrates a significant association between consumers’ buying intention and Perceived Usefulness (PU), Perceived Ease of Use (PEU), Perceived Enjoyment (PE), and Subjective Norms (SN). On the contrary, the data portrayed Perceived Risk (PR) as insignificant. However, our findings suggest that the TAM can still be used to explain the change in behavior associated with using a marketplace, particularly when buying online products or services. In addition, to give a more profound knowledge, various user characteristics according to generation group still need to be studied. Findings further suggest that this study has academic and industry ramifications regarding anticipating consumers’ online purchasing choices in the digital marketing community. The study concludes with a discussion of its limitations and future research directions.
Atrophy of the Posterior Cricoarytenoid Muscle as an Indicator of a Recurrent Laryngeal Nerve Injury History Before Revision Anterior Cervical Spine Surgery
Authors: Seok Sang Yun , Lee Dong-Ho , Lee Hyung Rae , Cho Jae Hwan , Hwang Chang Ju , Park Sehan
Published: September 2023

Study Design

Retrospective study.

Objectives

In our recent study, we observed some cases of symptomatic normal vocal cord motility instead of asymptomatic vocal cord palsy (VCP) in preoperative laryngoscopy of a revision anterior cervical spine surgery (ACSS) cohort. We assumed the intrinsic muscle atrophy caused by recurrent laryngeal nerve injury could cause vocal cord-related symptoms. Thus, radiological examinations were reviewed in relation to the posterior cricoarytenoid (PCA) muscle, one of the intrinsic muscles.

Methods

We retrospectively analyzed 64 patients who underwent a revision ACSS. Patients with vocal cord-related symptoms were classified as symptomatic group (group S, n = 11), and those without symptoms as asymptomatic group (group AS, n = 53). The bilateral size and signal intensity of the PCA muscles in these patients were measured in the axial view with preoperative computed tomography (CT) and magnetic resonance imaging (MRI) evaluations. Since the size and signal intensity values were different on each image, the ratios of the contralateral and ipsilateral muscle values were analyzed for each modality.

Results

There was no VCP on laryngoscopy study. However, the mean ratio of the PCA muscle size on CT was 1.40 ± .37 in group S and 1.02 ± .12 in group AS ( P = .007). These values on the MRI were 1.49 ± .45 in group S and 1.02 ± .14 in group AS, which was also a significant difference ( P = .008).

Conclusions

Evaluating the size of the PCA muscle before revision ACSS may predict a previous recurrent laryngeal nerve injury. Careful planning for the appropriate approach should be undertaken if vocal cord-related symptoms and atrophy of PCA muscle are evident.
Assessing the Agreement of Light Microscopic Evaluation of Oral Lichen Planus Lesions With Associated Direct Immunofluorescence Evaluation
Authors: Hansen Blake T , Payne Jeffrey B , Samson Kaeli K , Giannini Peter J
Published: September 2023

Aim/objective:

Assess agreement between light microscopy and direct immunofluorescence (DIF) for histopathologic evaluation of oral lichen planus (OLP).

Methods:

Records evaluated included 60 OLP, 16 lichenoid mucositis (LM), and 56 non-OLP/non-LM cases. Cases had both light microscopic and DIF evaluations. Histopathologic parameters of OLP included: (1) hydropic degeneration of the basal cell layer, (2) band-like lymphocytic infiltrate immediately subjacent to the epithelium, and (3) presence of Civatte bodies. Two calibrated examiners independently assessed light microscopic features. Examiners reviewed cases with discordant diagnoses to determine a consensus diagnosis. Intra-rater reliability (IRR), sensitivity, specificity, positive, and negative predictive values (PPV and NPV) were determined.

Results:

Of 132 patients, 72.7% were female, average age 61.9 (SD = 13.8). Most common sites were gingiva (37.9%), buccal mucosa (37.1%), and tongue (7.6%). IRR was 0.74 (95% CI: 0.40, 1.00) for the consensus diagnosis and 0.73 (95% CI: 0.39, 1.00) and 0.34 (95% CI: −0.03, 0.72) for the 2 examiners. Comparing consensus and definitive diagnoses: sensitivity of light microscopy: 0.32 (95% CI: 0.20, 0.45); specificity: 0.88 (95% CI: 0.78, 0.94); PPV: 0.68 (95% CI: 0.48, 0.84), and NPV: 0.61 (95% CI: 0.51, 0.70).

Conclusion:

Light microscopy alone is not a viable alternative to adjunctive DIF for diagnosis of OLP lesions.
High Positivity Rate of Urinary Mycobacterium tuberculosis Antigens Cocktail (ESAT-6, CFP-10, and MPT-64) in Active Tuberculosis Patients With and Without Human Immunodeficiency Virus Infection: A Cross-Sectional Study
Authors: Turbawaty Dewi Kartika , Surdjaja Novie Rahmawati , Indrati Agnes Rengga , Lismayanti Leni , Logito Verina
Published: September 2023

Introduction:

Human immunodeficiency virus (HIV) infection is a risk factor for the occurrence of a large of Mycobacterium tuberculosis (Mtb) antigen load in the body. The antigens cocktail namely early secretory antigenic target protein 6-kDa (ESAT-6), Culture filtrate protein 10 kDa (CFP-10), and Mycobacterium tuberculosis protein 64 (MPT-64) are secreted by Mtb during replication, hence, their concentration increase in patients with active Tuberculosis (TB). This increased levels facilitates their entry into the systemic circulation, followed by secretion by the glomerulus into the urine. The aim of this study was to determine the positivity rate of the urinary Mtb antigens cocktail between TB patients with and without HIV infection.

Methods:

This is an observational descriptive comparative study conducted with a cross-sectional design. Random urine samples were collected from patients diagnosed with active TB in Dr. Hasan Sadikin Bandung Hospital in 2021. The subjects were divided into 2 groups, TB-HIV group and TB without HIV group. The samples were tested using the quantitative immunochromatography method.

Result:

Sixty active TB patients consisting of TB patients with HIV infection (n = 30) and TB patients without HIV infection (n = 30). The positivity in the urinary Mtb antigens cocktail was 93.3% for TB-HIV group and 100% for TB without HIV group ( P = .492). The median concentration of urinary Mtb antigens cocktail in TB patients without HIV infection was higher than that of TB patients with HIV infection (137.73 ng/mL vs 96.69 ng/mL, respectively; P = .001).

Conclusion:

There was no significant difference in the positivity rate, meanwhile, there was a significant difference in concentration of the urinary Mtb antigens cocktail between active TB patients with and without HIV infection. Interestingly, this urinary Mtb antigens cocktail can be found in both groups without being affected by the patient’s immune condition, thus becoming a test to assist diagnose active TB.
BiocMAP: a Bioconductor-friendly, GPU-accelerated pipeline for bisulfite-sequencing data
Authors: Eagles Nicholas J. , Wilton Richard , Jaffe Andrew E. , Collado-Torres Leonardo
Published: September 2023

Background

Bisulfite sequencing is a powerful tool for profiling genomic methylation, an epigenetic modification critical in the understanding of cancer, psychiatric disorders, and many other conditions. Raw data generated by whole genome bisulfite sequencing (WGBS) requires several computational steps before it is ready for statistical analysis, and particular care is required to process data in a timely and memory-efficient manner. Alignment to a reference genome is one of the most computationally demanding steps in a WGBS workflow, taking several hours or even days with commonly used WGBS-specific alignment software. This naturally motivates the creation of computational workflows that can utilize GPU-based alignment software to greatly speed up the bottleneck step. In addition, WGBS produces raw data that is large and often unwieldy; a lack of memory-efficient representation of data by existing pipelines renders WGBS impractical or impossible to many researchers.

Results

We present BiocMAP, a Bioconductor-friendly methylation analysis pipeline consisting of two modules, to address the above concerns. The first module performs computationally-intensive read alignment using Arioc, a GPU-accelerated short-read aligner. Since GPUs are not always available on the same computing environments where traditional CPU-based analyses are convenient, the second module may be run in a GPU-free environment. This module extracts and merges DNA methylation proportions—the fractions of methylated cytosines across all cells in a sample at a given genomic site. Bioconductor-based output objects in R utilize an on-disk data representation to drastically reduce required main memory and make WGBS projects computationally feasible to more researchers.

Conclusions

BiocMAP is implemented using Nextflow and available at http://research.libd.org/BiocMAP/. To enable reproducible analysis across a variety of typical computing environments, BiocMAP can be containerized with Docker or Singularity, and executed locally or with the SLURM or SGE scheduling engines. By providing Bioconductor objects, BiocMAP’s output can be integrated with powerful analytical open source software for analyzing methylation data.
A scaffolded and annotated reference genome of giant kelp (Macrocystis pyrifera)
Authors: Diesel Jose , Molano Gary , Montecinos Gabriel J. , DeWeese Kelly , Calhoun Sara , Kuo Alan , Lipzen Anna , Salamov Asaf , Grigoriev Igor V. , Reed Daniel C. , Miller Robert J. , Nuzhdin Sergey V. , Alberto Filipe
Published: September 2023

Macrocystis pyrifera (giant kelp), is a brown macroalga of great ecological importance as a primary producer and structure-forming foundational species that provides habitat for hundreds of species. It has many commercial uses (e.g. source of alginate, fertilizer, cosmetics, feedstock). One of the limitations to exploiting giant kelp’s economic potential and assisting in giant kelp conservation efforts is a lack of genomic tools like a high quality, contiguous reference genome with accurate gene annotations. Reference genomes attempt to capture the complete genomic sequence of an individual or species, and importantly provide a universal structure for comparison across a multitude of genetic experiments, both within and between species. We assembled the giant kelp genome of a haploid female gametophyte de novo using PacBio reads, then ordered contigs into chromosome level scaffolds using Hi-C. We found the giant kelp genome to be 537 MB, with a total of 35 scaffolds and 188 contigs. The assembly N50 is 13,669,674 with GC content of 50.37%. We assessed the genome completeness using BUSCO, and found giant kelp contained 94% of the BUSCO genes from the stramenopile clade. Annotation of the giant kelp genome revealed 25,919 genes. Additionally, we present genetic variation data based on 48 diploid giant kelp sporophytes from three different Southern California populations that confirms the population structure found in other studies of these populations. This work resulted in a high-quality giant kelp genome that greatly increases the genetic knowledge of this ecologically and economically vital species.
Temporal variation in oral microbiome composition of patients undergoing autologous hematopoietic cell transplantation with keratinocyte growth factor
Authors: Bohn Bruno , Chalupova Miroslava , Staley Christopher , Holtan Shernan , Maakaron Joseph , Bachanova Veronika , El Jurdi Najla
Published: September 2023

Introduction

Autologous hematopoietic cell transplantation (AHCT) is a well-established treatment for lymphoma. Unintended effects of this therapy include oral mucositis (OM) and gastrointestinal toxicities, resulting in poor clinical outcomes. The gut microbiome has been previously linked to transplant toxicities among allogeneic recipients, but little is known about the effects of AHCT on the oral microbiome.

Methods

Seven patients with non-Hodgkin or Hodgkin lymphoma undergoing AHCT with palifermin (keratinocyte growth factor) were included. Buccal swab samples were collected at baseline and 14- and 28-days post-treatment. Oral microbial communities were characterized with 16 S rRNA amplicon sequencing. Temporal trends in community composition, alpha diversity, and beta diversity were investigated.

Results

A significant reduction in the relative abundance of the genera Gemella and Actinomyces were observed from baseline. No significant temporal differences in alpha diversity were observed. Significant changes in beta diversity were recorded.

Conclusion

Results of this pilot study suggest treatment with AHCT and palifermin affects the oral microbiome, resulting in temporal shifts in oral microbial community composition. Future studies are warranted to confirm these trends and further investigate the effects of AHCT on the oral microbiome and how these shifts may affect health outcomes.
Analysis of the association between dietary patterns and nonalcoholic fatty liver disease in a county in Guangxi
Authors: Xiao Song , Chen Ziqi , Mai Tingyu , Cai Jiansheng , Chen Yulu , Tang Xu , Gou Ruoyu , Luo Tingyu , He Kailian , Li Tingjun , Qin Jian , Zhang Zhiyong , Li You
Published: September 2023

Background

This study aims to investigate the relationship between different dietary patterns and non-alcoholic fatty liver disease (NAFLD).

Methods

Residents over 30 years old in the ecological longevity cohort in Gongcheng Yao Autonomous County, Guangxi Province were the research objects selected from 2018 to 2019. Physical examination, baseline population survey, and food frequency questionnaire (FFQ) survey were conducted. Dietary patterns were analyzed by factor analysis. Influencing factors of NAFLD were analyzed by multiple logistic regression.

Results

NAFLD was diagnosed in 241 of 2664 participants based on ultrasonography, and the detection rate was 9.0%. Factor analysis yielded a total of three dietary patterns, namely, traditional Chinese, Western, and cereal-potato dietary patterns. Results of multivariate logistic regression analysis showed that after adjusting for confounding factors, participants in the highest quartile of the Western dietary pattern exhibited a higher prevalence of NAFLD (OR = 2.799; 95% CI: 1.620–4.837; p < 0.05) than participants in the lowest quartile. Participants in the highest quartile of the cereal-potato pattern exhibited a decreased risk of NAFLD compared with those in the lowest quartile (OR = 0.581; 95% CI: 0.371–0.910, p < 0.05). The traditional Chinese patterns did not show any association with the risk of NAFLD.

Conclusions

The Western dietary pattern increases the risk of NAFLD, whereas the cereal-potato dietary pattern reduces the risk of NAFLD. It is important for the prevention and control of NAFLD to adhere to the cereal-potato dietary.
Clinical Data based XGBoost Algorithm for infection risk prediction of patients with decompensated cirrhosis: a 10-year (2012–2021) Multicenter Retrospective Case-control study
Authors: Zheng Jing , Li Jianjun , Zhang Zhengyu , Yu Yue , Tan Juntao , Liu Yunyu , Gong Jun , Wang Tingting , Wu Xiaoxin , Guo Zihao
Published: September 2023

Objectives

To appraise effective predictors for infection in patients with decompensated cirrhosis (DC) by using XGBoost algorithm in a retrospective case-control study.

Methods

Clinical data were retrospectively collected from 6,648 patients with DC admitted to five tertiary hospitals. Indicators with significant differences were determined by univariate analysis and least absolute contraction and selection operator (LASSO) regression. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed infection risk prediction model with simple-tree XGBoost model. Finally, the simple-tree XGBoost model is compared with the traditional logical regression (LR) model. Performances of models were evaluated by area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity.

Results

Six features, including total bilirubin, blood sodium, albumin, prothrombin activity, white blood cell count, and neutrophils to lymphocytes ratio were selected as predictors for infection in patients with DC. Simple-tree XGBoost model conducted by these features can predict infection risk accurately with an AUROC of 0.971, sensitivity of 0.915, and specificity of 0.900 in training set. The performance of simple-tree XGBoost model is better than that of traditional LR model in training set, internal verification set, and external feature set (P < 0.001).

Conclusions

The simple-tree XGBoost predictive model developed based on a minimal amount of clinical data available to DC patients with restricted medical resources could help primary healthcare practitioners promptly identify potential infection.
PFAS concentrations in early and mid-pregnancy and risk of gestational diabetes mellitus in a nested case-control study within the ethnically and racially diverse PETALS cohort
Authors: Peterson Alicia K. , Zhu Yeyi , Fuller Sophia , Feng Juanran , Alexeeff Stacey , Mitro Susanna D. , Kannan Kurunthachalam , Robinson Morgan , Padula Amy , Ferrara Assiamira
Published: September 2023

Background

Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk.

Methods

In the PETALS pregnancy cohort, a nested case–control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR).

Results

PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant.

Conclusions

Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.
Evaluation of allylestrenol for clinical pregnancies in patients treated with assisted reproductive techniques: a retrospective, propensity score matched, observational study
Authors: Yu Yuexin , Yu Tingting , Ding Weiping , Xiu Yinling , Zhao Mengsi , Sun Kaixuan , Zhang Qian , Xu Xiaohang
Published: September 2023

Background

Allylestrenol is an oral progestogen being increasingly used for luteal phase support in assisted reproductive techniques. However, evidence of the clinical efficacy of allylestrenol in luteal phase support is lacking. Dydrogesterone is a representative drug used for luteal phase support, the efficacy of which has been clinically confirmed. As such, we aimed to compare the effects of allylestrenol with the standard dydrogesterone on clinical pregnancy rates and pregnancy outcomes.

Methods

This retrospective study included 3375 assisted reproductive technique cycles using either allylestrenol or dydrogesterone between January 2015 and March 2020. Patients using either allylestrenol or dydrogesterone were matched in a 1:1 ratio using propensity scores. The primary outcomes were clinical pregnancy rate and pregnancy outcomes.

Results

No significant difference was found in the clinical pregnancy rate (53.5% vs. 53.2%, P = 0.928) and pregnancy outcomes (all P > 0.05) between allylestrenol and dydrogesterone. Compared with dydrogesterone, the use of allylestrenol significantly reduced the rate of biochemical pregnancies (6.4% vs. 11.8%, P < 0.001) and multiple gestation rate (16.8% vs. 26.3%, P = 0.001). Moreover, endometrial thickness, morphology, and blood flow were significantly improved by allylestrenol treatment (all P < 0.05).

Conclusions

Allylestrenol exhibited similar effects on clinical pregnancy rates and pregnancy outcomes as dydrogesterone. Moreover, allylestrenol can significantly reduce the biochemical pregnancy rate and improve the endometrial receptivity.
Incidence rates of treated mental disorders before and during the COVID-19 pandemic—a nationwide study comparing trends in the period 2015 to 2021
Authors: Jensen Pia , Engdahl Bo , Gustavson Kristin , Lund Ingunn Olea , Pettersen Johanne Hagen , Madsen Christian , Hauge Lars Johan , Knudsen Ann Kristin Skrindo , Reneflot Anne , Brandlistuen Ragnhild Eek , Ask Helga , Nesvåg Ragnar
Published: September 2023

Background

There is a concern that exposure to psychosocial stressors during the COVID-19 pandemic may have led to a higher incidence of mental disorders. Thus, this study aimed to compare trends in incidence rates of depressive disorder, anxiety disorders, obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and eating disorders in primary- and specialist health care before (2015–2019) and during the COVID-19 pandemic (2020–2021).

Methods

We used aggregated population registry data to calculate incidence rates of mental disorders from primary- (The Norwegian Control and Payment of Health Reimbursements Registry (KUHR)) and specialist (The Norwegian Patient Registry (NPR)) health care. The analyses included all Norwegian residents aged 18–65 during the study period. Incident cases were defined as having no previous registration with the same mental disorder in KUHR (from 2006) or NPR (from 2008). We used linear prediction models and mean models to compare incidence rates and test trends before and during the pandemic.

Results

During the pandemic, the incidence rates among women were higher or as predicted for OCD in specialist health care and for eating disorders in both primary- and specialist health care. These findings were strongest among women aged 18–24 years. Incidence rates for depression and phobia/OCD among both genders in primary health care and phobic anxiety disorders among both genders in specialist health care were lower or as predicted.

Conclusion

The COVID-19 pandemic may have led to more women needing treatment for OCD and eating disorders in the Norwegian population. The decreased incidence rates for some disorders might indicate that some individuals either avoided seeking help or had improved mental health during the pandemic.
Modifiable risk factors for ventilator associated diaphragmatic dysfunction: a multicenter observational study
Authors: Pu Hong , Doig Gordon S. , Lv Yu , Wu Xiaoxiao , Yang Fu , Zhang Shurong , Liang Zongan , Zhou Yan , Kang Yan
Published: September 2023

Background

Diaphragmatic dysfunction is known to be associated with difficulties weaning from invasive mechanical ventilation and is related to worse patient outcomes yet our understanding of how to prevent diaphragmatic dysfunction remains incomplete. We examined potentially modifiable risk factors for diaphragmatic dysfunction and attempted to estimate benefits attributable to altering these modifiable risk factors.

Methods

This prospective multicenter observational study was undertaken in the general ICUs of two tertiary care teaching hospitals. Critically ill adults expected to receive invasive mechanical ventilation for at least 48 h were enrolled. Diaphragm function was assessed by ultrasound each study day, with dysfunction defined as thickening fraction less than 20%.

Results

From January to December 2019, 856 patients were screened and 126 patients were enrolled. Overall, 40.5% (51/126) of patients experienced diaphragmatic dysfunction during invasive mechanical ventilation. Patients with diaphragmatic dysfunction were more likely to develop ventilator associated pneumonia (risk difference [RD] + 12.9%, 95% Confidence Interval [CI] 1.4 to 24.4%, P = 0.028), were more likely to experience extubation failure (RD + 8.5%, 95% CI 0.4 to 16.6%, P = 0.039) and required a longer duration of invasive mechanical ventilation (RD + 1.3 days, 95% CI 0.1 to 2.5 days, P = 0.035). They also required a longer hospital stay (RD + 1.2 days, 95% CI 0.04 to 2.4 days, P = 0.041) and were more likely to die before hospital discharge (RD + 18.1%, 95% CI 3.7 to 32.5%, P = 0.014). Multivariable analysis considered the impact of age, sex, pre-existing nutritional status, caloric intake, amino acid intake, acute disease severity, modes of mechanical ventilation, measures of respiratory status, sedation, pain control and baseline diaphragm thickness. Only SOFA score (P = 0.008) and early amino acid intake (P = 0.001) remained significant independent risk factors for the onset of diaphragmatic dysfunction. Causal path modeling suggested early amino acid intake may significantly reduce diaphragmatic dysfunction (RRR 29%, 95% CI 10% to 48%, P = 0.003) and may also reduce mortality (RRR 49%, 95% CI 25% to 73%, P < 0.0001).

Conclusions

Amino acid intake during the first 24 h of ICU stay may represent an important, modifiable risk factor for diaphragmatic dysfunction and may have a direct causal effect on mortality. We recommend additional research on this topic.