bluuebunny/crossref_metadata_2025_split huggingface dataset:
NAMPT Haploinsufficiency Is a Therapeutic Vulnerability in High-Risk Myeloid Malignancies
Authors: Senagolage Madhavi D. , Khan Saira , Skuli Sarah , Carroll Martin , McNerney Megan E. 
Published: December 2023

Monosomy 7 (−7) and del7q are the most common high-risk cytogenetic abnormalities and occur across the spectrum of myeloid disorders. -7/del(7q) also co-occur with other high-risk factors such as mutations or deletion of TP53. Standard, non-specific chemotherapy drugs are less effective in these high-risk patients, resulting in a median survival rate of approximately one year. To identify novel, targeted agents for these neoplasms, we sought “collateral lethal” genes, i.e. essential, druggable genes encoded on chromosome 7 that are haploinsufficient upon their loss of heterozygosity.
To this end, we first identified essential genes located on chromosome 7. We mined genome-wide CRISPR/Cas9 screen data from 27 human acute myeloid leukemia (AML) cell lines within the DepMap database and identified 65 chromosome 7-encoded, candidate essential genes in AML. To determine those essential genes with known inhibitors, we intersected these 65 candidates with the Drug-Gene Interaction and canSAR.ai databases. We found that nicotinamide phosphoribosyltransferase ( NAMPT), the rate-limiting enzyme that catalyzes the first step of NAD + biosynthesis from nicotinamide, was one of four essential and druggable targets on chromosome 7. Notably, NAMPT was the only essential gene on chromosome 7 with a first-in-class orally bioavailable inhibitor, KPT 9274, currently in clinical trials (NCT04914845). Moreover, NAMPT DNA copy number, mRNA, and protein levels all negatively correlated with cell line sensitivity to NAMPT loss, implicating NAMPT as a collateral lethal candidate gene. We confirmed that isogenic human AML cell lines CRISPR-engineered to partially reduce NAMPT DNA copy led to reduced NAMPT protein levels, indicating NAMPT is a haploinsufficient gene. Cells with ~50% NAMPT levels were significantly more sensitive to the KPT 9274 treatment, and became less viable and more apoptotic, compared to control locus edited cells. To determine whether TP53 status could alter this vulnerability, we generated cell lines with both TP53 loss and 50% NAMPT loss. We found TP53 mutational status did not attenuate the observed effects of NAMPT inhibition on cell survival. Viability assays with primary patient AML samples confirmed that -7/del(7q) status imparts significantly elevated sensitivity to KPT 9274 treatment than samples with diploid chromosome 7 alleles.
In summary, our findings reveal NAMPT heterozygosity as a therapeutic vulnerability in high-risk myeloid neoplasms that warrants clinical follow-up. Further, we provide a framework centered on data-mining for uncovering collateral lethal genes in other cancers with recurrent chromosomal arm level deletions.
Model-based analysis of the incidence trends and transmission dynamics of COVID-19 associated with the Omicron variant in representative cities in China
Authors: Ma Yifei , Xu Shujun , Luo Yuxin , Li Jiantao , Lei Lijian , He Lu , Wang Tong , Yu Hongmei , Xie Jun 
Published: December 2023

Abstract
Background
In 2022, Omicron outbreaks occurred at multiple sites in China. It is of great importance to track the incidence trends and transmission dynamics of coronavirus disease 2019 (COVID-19) to guide further interventions.

Methods
Given the population size, economic level and transport level similarities, two groups of outbreaks (Shanghai vs. Chengdu and Sanya vs. Beihai) were selected for analysis. We developed the SEAIQRD, ARIMA, and LSTM models to seek optimal modeling techniques for waves associated with the Omicron variant regarding data predictive performance and mechanism transmission dynamics, respectively. In addition, we quantitatively modeled the impacts of different combinations of more stringent interventions on the course of the epidemic through scenario analyses.

Results
The best-performing LSTM model showed better prediction accuracy than the best-performing SEAIQRD and ARIMA models in most cases studied. The SEAIQRD model had an absolute advantage in exploring the transmission dynamics of the outbreaks. Regardless of the time to inflection point or the time to Rt curve below 1.0, Shanghai was later than Chengdu (day 46 vs. day 12/day 54 vs. day 14), and Sanya was later than Beihai (day 16 vs. day 12/day 20 vs. day 16). Regardless of the number of peak cases or the cumulative number of infections, Shanghai was higher than Chengdu (34,350 vs. 188/623,870 vs. 2,181), and Sanya was higher than Beihai (1,105 vs. 203/16,289 vs. 3,184). Scenario analyses suggested that upgrading control level in advance, while increasing the index decline rate and quarantine rate, were of great significance for shortening the time to peak and Rt below 1.0, as well as reducing the number of peak cases and final affected population.

Conclusions
The LSTM model has great potential for predicting the prevalence of Omicron outbreaks, whereas the SEAIQRD model is highly effective in revealing their internal transmission mechanisms. We recommended the use of joint interventions to contain the spread of the virus.
Comparative study of trimming and resection of diseased finger superficial flexor tendons in gouty carpal tunnel syndrome
Authors: Liu Jinquan , Gu Fengming , Liu Qianyuan , Chen Wenxuan , Ying Qiuwen , Xu Yi , Zhu Aiping , Tang Li , Jing Danfeng , Xu Zhonghua , Pan Xiaoyun , Mi Jingyi 
Published: December 2023

Abstract
Background
Hyperuricemia can lead to synovial hyperplasia in the wrist. In severe cases, it can lead to the deposition of gouty stone in the carpal tunnel, resulting in increased pressure in the carpal tunnel and compression of the median nerve to cause carpal tunnel syndrome (CTS), which is called gouty carpal tunnel syndrome (GCTS). As for the surgical treatment of gouty carpal tunnel syndrome, scholars have different opinions on whether it is necessary to remove the superficial flexor tendon. The purpose of this study was to compare the clinical efficacy of trimming and resection of the diseased superficial flexor tendon in the treatment of gouty carpal tunnel syndrome.

Methods
Clinical data were collected from May 2016 to July 2021 from 10 patients (13 affected wrists) diagnosed with gouty carpal tunnel syndrome and classified into two groups according to the surgical modality: the diseased portion of the gout-eroded superficial finger tendon was trimmed in 9 wrists, and the diseased superficial finger flexor tendon was excised in 4 wrists. Values related to flexion and extension functions, 2-PD, DASH, BCTQ, VAS and recurrence in the affected fingers were compared between the two groups as well as before and after surgery in each group.

Results
All affected limbs used were cleared of gouty stones, finger numbness improved, no skin necrosis occurred, and all incisions healed at stage I. At follow-up (13.58 ± 5.53 months), there was no significant difference between groups in flexion and extension function, 2-PD, DASH, BCTQ, and VAS with respect to the affected fingers, and patients in both groups improved significantly before and after surgery. Treatment of only one wrist involved trimming to remove lesion-affected portions of tendon, which reappeared 1 year after surgery, and there was one case of poor recovery from greater piriformis muscle atrophy in both procedures.

Conclusion
Regarding surgical treatment of patients with gouty carpal tunnel syndrome in which the gouty stone has invaded the superficial flexor tendons of the fingers, the diseased superficial flexor tendons can be selectively excised, and the postoperative mobility of the affected fingers may not be impaired.
Improving preoperative prediction of surgery duration
Authors: Riahi Vahid , Hassanzadeh Hamed , Khanna Sankalp , Boyle Justin , Syed Faraz , Biki Barbara , Borkwood Ellen , Sweeney Lianne 
Published: December 2023

Abstract
Background
Operating rooms (ORs) are one of the costliest units in a hospital, therefore the cumulative consequences of any kind of inefficiency in OR management lead to a significant loss of revenue for the hospital, staff dissatisfaction, and patient care disruption. One of the possible solutions to improving OR efficiency is knowing a reliable estimate of the duration of operations. The literature suggests that the current methods used in hospitals, e.g., a surgeon’s estimate for the given surgery or taking the average of only five previous records of the same procedure, have room for improvement.

Methods
We used over 4 years of elective surgery records (n = 52,171) from one of the major metropolitan hospitals in Australia. We developed robust Machine Learning (ML) approaches to provide a more accurate prediction of operation duration, especially in the absence of surgeon’s estimation. Individual patient characteristics and historic surgery information attributed to medical records were used to train predictive models. A wide range of algorithms such as Extreme Gradient Boosting (XGBoost) and Random Forest (RF) were tested for predicting operation duration.

Results
The results show that the XGBoost model provided statistically significantly less error than other compared ML models. The XGBoost model also reduced the total absolute error by 6854 min (i.e., about 114 h) compared to the current hospital methods.

Conclusion
The results indicate the potential of using ML methods for reaching a more accurate estimation of operation duration compared to current methods used in the hospital. In addition, using a set of realistic features in the ML models that are available at the point of OR scheduling enabled the potential deployment of the proposed approach.
A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
Authors: Samadi Pouria , Shahnazari Mina , Shekari Abolfazl , Maghool Fatemeh , Jalali Akram 
Published: December 2023

AbstractThe HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Here, based on the co-expression network analysis and construction of interacting lncRNA–mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1’s aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1’s engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8+ T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1’s potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The increased HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic strategy, and a focal point for immunotherapeutic interventions.
Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice
Authors: Zeng Xiaoyan , Cheung Stanley K. K. , Shi Mengqi , Or Penelope M. Y. , Li Zhining , Liu Julia Y. H. , Ho Wayne L. H. , Liu Tian , Lu Kun , Rudd John A. , Wang Yubing , Chan Andrew M. 
Published: December 2023

AbstractGlial cell-mediated neuroinflammation and neuronal attrition are highly correlated with cognitive impairment in Alzheimer’s disease. YKL-40 is a secreted astrocytic glycoprotein that serves as a diagnostic biomarker of Alzheimer’s disease. High levels of YKL-40 are associated with either advanced Alzheimer’s disease or the normal aging process. However, the functional role of YKL-40 in Alzheimer’s disease development has not been firmly established. In a 5xFAD mouse model of Alzheimer’s disease, we observed increased YKL-40 expression in the cerebrospinal fluid of 7-month-old mice and was correlated with activated astrocytes. In primary astrocytes, Aβ1-42 upregulated YKL-40 in a dose-dependent manner and was correlated with PI3-K signaling pathway activation. Furthermore, primary neurons treated with YKL-40 and/or Aβ1-42 resulted in significant synaptic degeneration, reduced dendritic complexity, and impaired electrical parameters. More importantly, astrocyte-specific knockout of YKL-40 over a period of 7 days in symptomatic 5xFAD mice could effectively reduce amyloid plaque deposition in multiple brain regions. This was also associated with attenuated glial activation, reduced neuronal attrition, and restored memory function. These biological phenotypes could be explained by enhanced uptake of Aβ1-42 peptides, increased rate of Aβ1-42 degradation and acidification of lysosomal compartment in YKL-40 knockout astrocytes. Our results provide new insights into the role of YKL-40 in Alzheimer’s disease pathogenesis and demonstrate the potential of targeting this soluble biomarker to alleviate cognitive defects in symptomatic Alzheimer’s disease patients.
Impact of NAD+ metabolism on ovarian aging
Authors: Liang Jinghui , Huang Feiling , Song Zhaoqi , Tang Ruiyi , Zhang Peng , Chen Rong 
Published: December 2023

AbstractNicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular redox reactions, is closely associated with age-related functional degeneration and metabolic diseases. NAD exerts direct and indirect influences on many crucial cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cellular senescence, and immune cell functionality. These cellular processes and functions are essential for maintaining tissue and metabolic homeostasis, as well as healthy aging. Causality has been elucidated between a decline in NAD levels and multiple age-related diseases, which has been confirmed by various strategies aimed at increasing NAD levels in the preclinical setting. Ovarian aging is recognized as a natural process characterized by a decline in follicle number and function, resulting in decreased estrogen production and menopause. In this regard, it is necessary to address the many factors involved in this complicated procedure, which could improve fertility in women of advanced maternal age. Concerning the decrease in NAD+ levels as ovarian aging progresses, promising and exciting results are presented for strategies using NAD+ precursors to promote NAD+ biosynthesis, which could substantially improve oocyte quality and alleviate ovarian aging. Hence, to acquire further insights into NAD+ metabolism and biology, this review aims to probe the factors affecting ovarian aging, the characteristics of NAD+ precursors, and the current research status of NAD+ supplementation in ovarian aging. Specifically, by gaining a comprehensive understanding of these aspects, we are optimistic about the prominent progress that will be made in both research and therapy related to ovarian aging.
Ethnobotanical contributions to global fishing communities: a review
Authors: Mendoza Jimlea Nadezhda , Hanazaki Natalia , Prūse Baiba , Martini Agnese , Bittner Maria Viktoria , Kochalski Sophia , Macusi Edison , Ciriaco Aimee , Mattalia Giulia , Sõukand Renata 
Published: December 2023

Abstract
Background
Ethnobotanical knowledge about the role of plants in fisheries provides valuable ecological information vital for sustainable management of local resources; however, it is diluted and understudied globally. This literature review aims to map the knowledge of plant use within traditional fishing communities.

Methods
Through the PRISMA method, we identified and selected 34 articles reporting the use of plants in fisheries, and including 344 taxa of plants and algae. Uses of plants and algae were grouped into different categories.

Results
In the novel categorization of fishery-related uses we proposed, the most mentioned were for fishing and building/repair of fishing artifacts and habitat-related uses, while the records of plants related to fiber uses, providing aid in fishing management and species causing problems, were among the least mentioned. Semi-structured interview is most commonly used with local resource users, especially fishery experts, in exploring perceptions on plant use within traditional fishing communities. Diversity was high in all the recorded families, but most were reported locally.

Conclusion
Ethnobotanical studies with fishers are not common in the documented literature but they provide a large number of use reports. On the basis this review, in most of the world, the information is of a casual and sporadic nature. Fishers can provide information on aquatic plants and algae that create problems and aid in fishing management, which are crucial in understanding the ecosystem of a region experiencing environmental challenges. This knowledge is greatly understudied globally and undergoing a rapid decline, as highlighted in several of the reviewed articles. Thus, further systematic research on fishery-related uses of plants by fisherfolk is needed considering its potential contribution to the sustainable management of fishery resources.
An efficient screening system of disease-resistant genes from wild apple, Malus sieversii in response to Valsa mali pathogenic fungus
Authors: Wen Xuejing , Yuan Jiangxue , Bozorov Tohir A. , Waheed Abdul , Kahar Gulnaz , Haxim Yakupjan , Liu Xiaojie , Huang Lili , Zhang Daoyuan 
Published: December 2023

AbstractFor molecular breeding of future apples, wild apple (Malus sieversii), the primary progenitor of domesticated apples, provides abundant genetic diversity and disease-resistance traits. Valsa canker (caused by the fungal pathogen Valsa mali) poses a major threat to wild apple population as well as to cultivated apple production in China. In the present study, we developed an efficient system for screening disease-resistant genes of M. sieversii in response to V. mali. An optimal agrobacterium-mediated transient transformation of M. sieversii was first used to manipulate in situ the expression of candidate genes. After that, the pathogen V. mali was inoculated on transformed leaves and stems, and 3 additional methods for slower disease courses were developed for V. mali inoculation. To identify the resistant genes, a series of experiments were performed including morphological (incidence, lesion area/length, fungal biomass), physiological (H2O2 content, malondialdehyde content), and molecular (Real-time quantitative Polymerase Chain Reaction) approaches. Using the optimized system, we identified two transcription factors with high resistance to V. mali, MsbHLH41 and MsEIL3. Furthermore, 35 and 45 downstream genes of MsbHLH41 and MsEIL3 were identified by screening the V. mali response gene database in M. sieversii, respectively. Overall, these results indicate that the disease-resistant gene screening system has a wide range of applications for identifying resistant genes and exploring their immune regulatory networks.
Efficacy of acupuncture combined with active exercise training in improving pain and function of knee osteoarthritis individuals: a systematic review and meta-analysis
Authors: Chen Jia , Guo Hong , Pan Juanhong , Li Hongpeng , Wang Yongshen , Liu Zhixiang , Xie Yulong , Jin Song 
Published: December 2023

Abstract
Objective
To conduct a systematic review and meta-analysis to investigate the clinical efficacy of acupuncture combined with active exercise training in improving pain and function of knee osteoarthritis (KOA) individuals.

Data sources
PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Data, Technology Periodical Database and China Biology Medicine were searched from their inceptions to April 5, 2023.

Review methods
We analyzed trials of acupuncture combined with active exercise training for KOA. The included studies were of high quality (Jadad ≥ 4) and RCTs. Study selection, data extraction, risk of bias and quality assessment were independently performed by two reviewers. We performed systematic analyses based on different outcome measures, including total efficiency rate, visual analogue scale (VAS), the Western Ontario and Mcmaster Universities Osteoarthritis Index (WOMAC), the Lysholm Knee Scale (LKS) and range of motion (ROM). We used Review Manager 5.3 and Stata/MP 14.0 to analyze the data. And it was verified by trial sequence analysis (TSA). If I2 > 50% and p < 0.05, we performed sensitivity analysis and subgroup analysis to find the source of heterogeneity. Publication bias was studied by funnel plot and Egger’s test was used to verify it.

Results
Full 11 high-quality studies (Jadad ≥ 4) including 774 KOA individuals were included in this review for meta-analysis. The results showed that acupuncture combined with active exercise training (combined group) was superior to the acupuncture group in improving the total effective rate [RR = 1.13, 95%CI (1.05, 1.22), I2 = 0%, P = 0.70], reducing the pain level (VAS) [MD = − 0.74, 95%CI (− 1.04,  − 0.43), I2 = 68%, P < 0.05], improving knee joint function (WOMAC) [MD =  − 6.97, 95%CI (− 10.74, − 3.19), I2 = 76%, P < 0.05] and improving joint range of motion (ROM) [MD = 6.25, 95%CI (2.37, 10.04), I2 = 0%, P = 0.71]. Similarly, the combined group showed significant improvements in the total effective rate [RR = 1.31, 95% CI (1.18, 1.47), I2 = 48%, P = 0.10], pain (VAS) [MD = 1.42, 95% CI (− 1.85, − 1.00), I2 = 65%, P = 0.02] and knee function (WOMAC) [MD = 7.05, 95% CI (− 11.43, − 2.66), I2 = 86%, P < 0.05] compared with the non-acupuncture group.

Conclusion
The combined effect of all studies showed significant benefits of acupuncture combined with active exercise training in improving the total effective rate, reducing pain, promoting recovery of knee function and expanding range of motion. However, some evaluation indicators are highly subjective and need to be further confirmed by more objective and evidence-based high-quality RCTs in future.
Systematic Review Registration: [PROSPERO], identifier [No. CRD42023425823].