bluuebunny/crossref_metadata_2025_split huggingface dataset:
First assistant experience in total laparoscopic pancreaticoduodenectomy: accelerating the learning curve for an operator
Authors: Li Dongrui , Du Chengxu , Wang Wenbin , Zhang Jiansheng , Liu Jianhua 
Published: April 2023

Abstract
Objective
Compare and analyze clinical data of total laparoscopic pancreaticoduodenectomy (TLPD) cases for surgeons with / without first assistant experience (FAE) in TLPD. Probe influence of FAE in TLPD on the learning curve for an operator.

Methods
The clinical data of 239 patients, that underwent TLPD performed by two surgeons between January 2017 and January 2022) in our department, were consecutively collected and divided into two groups (A and B). Group A cases were operated by Surgeon A, with FAE of 57 TLPDs in our department prior to initial TLPD as an operator. Group B cases were operated by Surgeon B with no FAE of TLPD. Cumulative sum (CUSUM) method developed learning curves. Clinical data and both surgeons’ learning curves were statistically compared between both groups.

Results
Between both groups, no statistically significant variations were observed for pre-operative health conditions. Reduced surgical duration, blood loss and transfusion volume during surgery, together with reductions in major post–operative complication rates and reduced hospital/ICU stays were identified within Group A, having statistically significant variations. The technical plateau phases of the learning curves were approximately 25–41 cases and 35–51 cases, for Surgeon A and Surgeon B, respectively.

Conclusion
FAE in TLPD can accelerate the learning curve of TLPD for an operator, with safer surgical procedures and enhanced post–operative recovery.
How does ethnicity affect presence of advance care planning in care records for individuals with advanced disease? A mixed-methods systematic review
Authors: Crooks Jodie , Trotter Sophie ,   Patient Public Involvement Consortium, OBE Ruby Bhatti , Monaghan Elizabeth , Clarke Gemma 
Published: April 2023

Abstract
Background
Advance care planning (ACP) is the process supporting individuals with life-limiting illness to make informed decisions about their future healthcare. Ethnic disparities in ACP have been widely highlighted, but interpretation is challenging due to methodological heterogeneity. This review aims to examine differences in the presence of documented ACP in individuals’ care records for people with advanced disease by ethnic group, and identify patient and clinician related factors contributing to this.

Methods
Mixed-methods systematic review. Keyword searches on six electronic databases were conducted (01/2000–04/2022). The primary outcome measure was statistically significant differences in the presence of ACP in patients’ care records by ethnicity: quantitative data was summarised and tabulated. The secondary outcome measures were patient and clinician-based factors affecting ACP. Data was analysed qualitatively through thematic analysis; themes were developed and presented in a narrative synthesis. Feedback on themes was gained from Patient and Public Involvement (PPI) representatives. Study quality was assessed through Joanna Briggs Institute Critical Appraisal tools and Gough’s Weight of Evidence.

Results
N=35
papers were included in total; all had Medium/High Weight of Evidence. Fifteen
papers (comparing two or more ethnic groups) addressed the primary outcome
measure. Twelve of the fifteen papers reported White patients had statistically
higher rates of formally documented ACP in their care records than patients
from other ethnic groups. There were no significant differences in the presence
of informal ACP between ethnic groups. Nineteen papers addressed the secondary
outcome measure; thirteen discussed patient-based factors impacting ACP
presence with four key themes: poor awareness and understanding of ACP; financial
constraints; faith and religion; and family involvement. Eight papers discussed
clinician-based factors with three key themes: poor clinician confidence around
cultural values and ideals; exacerbation of institutional constraints; and
pre-conceived ideas of patients’ wishes.

Conclusions
This review found differences in the presence of legal ACP across ethnic groups despite similar presence of informal end of life conversations. Factors including low clinician confidence to deliver culturally sensitive, individualised conversations around ACP, and patients reasons for not wishing to engage in ACP (including, faith, religion or family preferences) may begin to explain some documented differences.

Trial registration
PROSPERO-CRD42022315252.
Early clinical exposure in medical education: the experience from Debre Tabor University
Authors: Ewnte Biniam , Yigzaw Tegbar 
Published: April 2023

Abstract
Background
The idea of early clinical exposure in Ethiopian medical schools is a young concept. Old and newly established universities across the nation are shifting towards incorporation of early clinical exposure (ECE) in their curricula. Debre Tabor University introduced ECE in undergraduate medical education from inception. This study generated evidence on students’ experience and academic leaders’ reflection on early clinical exposure implementation.

Objective
This study was carried out to investigate medical students’ perception towards early clinical exposure and its implementation process by instructors in undergraduate medical education at Debre Tabor University.

Method
A cross-sectional survey design that combines quantitative and qualitative methods was conducted in 2021. We asked fifth year medical students (42) to complete a self-administered questionnaire on 5-point Likert scale. The data were supplemented by semi-structured interview with 6 purposively selected academic leaders on the factors that facilitate or impede early clinical exposure implementation. The quantitative data were entered and analyzed using SPSS 20 to compute frequency, median and interquartile range. The qualitative data were analyzed thematically.

Results
The study findings suggest that early clinical exposure (ECE) has a positive impact on the development of students’ professional knowledge, problem-solving skills, motivation, active learning, and community orientation. Specifically, 64.3% of the surveyed students believed that ECE was effective in constructing their professional knowledge, while 52.4% felt that it improved their problem-solving skills and facilitated constructive/active learning. Additionally, 57.1% of students reported that ECE improved their motivation and 50% noted that it facilitated community orientation. The study also identified several barriers to the implementation of ECE, with the heavy workload being the most commonly mentioned (78.6%). Other challenges included a loose linkage between academic and healthcare institutions (59.5%) and a lack of orientation on the implementation process (35.7%). Academic leaders reflected that ECE was beneficial in familiarizing students with the clinical environment, but staff commitment was crucial for its successful implementation. The study also found that heavy workload, lack of assessment dedicated to ECE on the curriculum, and poorly oriented staff about the program impeded its implementation.

Conclusion and recommendations
The findings of this study suggest that early clinical exposure was beneficial learning method. Teachers’ commitment to their roles with adequate preparation, and the contribution of curriculum in providing the learning objective and cases for each session were factors that facilitate effective implementation of ECE. Heavy workload and poor orientation about the program could impede ECE implementation.
Phylogenomics of the Olea europaea complex using 15 whole genomes supports recurrent genetic admixture together with differentiation into seven subspecies
Authors: Julca Irene , Vargas Pablo , Gabaldón Toni 
Published: April 2023

AbstractBackgroundThe last taxonomic account ofOlearecognises six subspecies withinOlea europaeaL., including the Mediterranean olive tree (subsp.europaea) and five other subspecies (laperrinei,guanchica,maroccana,cerasiformis, andcuspidata) distributed across the Old World, including Macaronesian islands. The evolutionary history of this monophyletic group (O. europaeacomplex) has revealed a reticulated scenario involving hybridization and polyploidization events, leading to the presence of a polyploid series associated with the subspecies. However, how the polyploids originated, and how the different subspecies contributed to the domestication of the cultivated olive are questions still debated. Tracing the recent evolution and genetic diversification of the species is key for the management and preservation of its genetic resources. To study the recent history of theO. europaeacomplex, we compared newly sequenced and available genomes for 27 individuals representing the six subspecies.ResultsOur results show discordance between current subspecies distributions and phylogenomic patterns, which support intricate biogeographic patterns. The subspeciesguanchica, restricted to the Canary Islands, is closely related to subsp.europaea, and shows a high genetic diversity. The subsp.laperrinei, restricted now to high mountains of the Sahara desert, and the Canarian subsp.guanchicacontributed to the formation of the allotetraploid subsp.cerasiformis(Madeira islands) and the allohexaploid subsp.maroccana(western Sahara region). Our phylogenomic data support the recognition of one more taxon (subsp.ferruginea) for the Asian populations, which is clearly segregated from the African subsp.cuspidata.ConclusionsIn sum, theO. europaeacomplex underwent several processes of hybridization, polyploidy, and geographical isolation resulting in seven independent lineages with certain morphological traits recognised into subspecies.
Haplotype-resolved genomes of two buckwheat crops provide insights into their contrasted rutin concentrations and reproductive systems
Authors: Lin Hao , Yao Yingjun , Sun Pengchuan , Feng Landi , Wang Shuo , Ren Yumeng , Yu Xi , Xi Zhengxiang , Liu Jianquan 
Published: April 2023

AbstractBackgroundTwo widely cultivated annual buckwheat crops,Fagopyrum esculentumandF. tataricum, differ from each other in both rutin concentration and reproductive system. However, the underlying genetic mechanisms remain poorly elucidated.ResultsHere, we report the first haplotype-resolved chromosome-level genome assemblies of the two species. Two haplotype genomes ofF. esculentumwere assembled as 1.23 and 1.19 Gb with N50 = 9.8 and 12.4 Mb, respectively; the two haplotype genomes ofF. tataricumwere 453.7 and 446.2 Mb with N50 = 50 and 30 Mb, respectively. We further annotated protein-coding genes of each haplotype genome based on available gene sets and 48 newly sequenced transcriptomes. We found that more repetitive sequences, especially expansion of long terminal repeat retrotransposons (LTR-RTs), contributed to the large genome size ofF. esculentum. Based on the well-annotated sequences, gene expressions, and luciferase experiments, we identified the sequence mutations of the promoter regions of two key genes that are likely to have greatly contributed to the high rutin concentration and selfing reproduction inF. tartaricum.ConclusionsOur results highlight the importance of high-quality genomes to identify genetic mutations underlying phenotypic differences between closely related species.F. tataricummay have been experienced stronger selection thanF. esculentumthrough choosing these two non-coding alleles for the desired cultivation traits. These findings further suggest that genetic manipulation of the non-coding promoter regions could be widely employed for breeding buckwheat and other crops.
Fear-of-intimacy-mediated zinc transport is required for Drosophila fat body endoreplication
Authors: Ji Xiaowen , Gao Jiajia , Wei Tian , Jin Li , Xiao Guiran 
Published: April 2023

Abstract
Background
Endoreplication is involved in the development and function of many organs, the pathologic process of several diseases. However, the metabolic underpinnings and regulation of endoreplication have yet to be well clarified.

Results
Here, we showed that a zinc transporter fear-of-intimacy (foi) is necessary for Drosophila fat body endoreplication. foi knockdown in the fat body led to fat body cell nuclei failure to attain standard size, decreased fat body size and pupal lethality. These phenotypes could be modulated by either altered expression of genes involved in zinc metabolism or intervention of dietary zinc levels. Further studies indicated that the intracellular depletion of zinc caused by foi knockdown results in oxidative stress, which activates the ROS-JNK signaling pathway, and then inhibits the expression of Myc, which is required for tissue endoreplication and larval growth in Drosophila.

Conclusions
Our results indicated that FOI is critical in coordinating fat body endoreplication and larval growth in Drosophila. Our study provides a novel insight into the relationship between zinc and endoreplication in insects and may provide a reference for relevant mammalian studies.
A TMVP1-modified near-infrared nanoprobe: molecular imaging for tumor metastasis in sentinel lymph node and targeted enhanced photothermal therapy
Authors: Wang Xueqian , Dai Geyang , Jiang Guiying , Zhang Danya , Wang Ling , Zhang Wen , Chen Huang , Cheng Teng , Zhou Ying , Wei Xiao , Li Fei , Ma Ding , Tan Songwei , Wei Rui , Xi Ling 
Published: April 2023

Abstract
Background
TMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging.

Results
In this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine.

Conclusion
TMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis.
Maternal exposure to ultrafine particles enhances influenza infection during pregnancy
Authors: Drury Nicholas L. , Mustapha Toriq , Shore Ross A. , Zhao Jiayun , Wright Gus A. , Hoffmann Aline Rodrigues , Talcott Susanne U. , Regan Annette , Tighe Robert M. , Zhang Renyi , Johnson Natalie M. 
Published: April 2023

Abstract
Background
Interactions between air pollution and infectious agents are increasingly recognized and critical to identify, especially to protect vulnerable populations. Pregnancy represents a vulnerable period for influenza infection and air pollution exposure, yet interactions during pregnancy remain unclear. Maternal exposure to ultrafine particles (UFPs, $$\le$$
≤
100 nm diameter), a class of particulate matter ubiquitous in urban environments, elicits unique pulmonary immune responses. We hypothesized that UFP exposure during pregnancy would lead to aberrant immune responses to influenza enhancing infection severity.

Results
Building from our well-characterized C57Bl/6N mouse model employing daily gestational UFP exposure from gestational day (GD) 0.5–13.5, we carried out a pilot study wherein pregnant dams were subsequently infected with Influenza A/Puerto Rico/8/1934 (PR8) on GD14.5. Findings indicate that PR8 infection caused decreased weight gain in filtered air (FA) and UFP-exposed groups. Co-exposure to UFPs and viral infection led to pronounced elevation in PR8 viral titer and reduced pulmonary inflammation, signifying potential suppression of innate and adaptive immune defenses. Pulmonary expression of the pro-viral factor sphingosine kinase 1 (Sphk1) and pro-inflammatory cytokine interleukin-1β (IL-1$$\beta$$
β
) was significantly increased in pregnant mice exposed to UFPs and infected with PR8; expression correlated with higher viral titer.

Conclusions
Results from our model provide initial insight into how maternal UFP exposure during pregnancy enhances respiratory viral infection risk. This model is an important first step in establishing future regulatory and clinical strategies for protecting pregnant women exposed to UFPs.
A study on the anti-osteoporosis mechanism of isopsoralen based on network pharmacology and molecular experiments
Authors: Wang Jian , Chen Tianyu , Li Xiang , Zhang Yu , Fu Shuang , Huo Ruikun , Duan Yan 
Published: April 2023

Abstract
Objective
Osteoporosis (OP) is a disease caused by multiple factors. Studies have pointed out that isopsoralen (IPRN) is one of the most effective drugs for the treatment of OP. Based on network pharmacological and molecular experimental analysis, the molecular mechanism of IPRN in osteoporosis is clarified.

Methods
IPRN target genes and OP-related genes were predicted from the databases. Intersections were obtained and visualized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on target genes, which was confirmed by experiments internal and external experiments. Molecular docking was used to verify the binding between IPRN and target proteins. Molecular dynamics (MD) simulates the binding affinity of protein targets and active compounds.

Results
87 IPRN target genes and 242 disease-related targets were predicted. The protein–protein interaction (PPI) network identified 18 IPRN target proteins for the treatment of OP. GO analysis indicated that target genes were involved in biological processes. KEGG analysis showed that pathways such as PI3K/AKT/mTOR were associated with OP. Cell experiments (qPCR and WB) found that the expressions of PI3K, AKT, and mTOR in MC3T3-E1 cells at 10 μM, 20 μM, and 50 μM IPRN concentrations, especially at 20 μM IPRN treatment, were higher than those in the control group at 48 h. Animal experiments also showed that compared with the control group, 40 mg/kg/time IPRN could promote the expression of the PI3K gene in chondrocytes of SD rats.

Conclusions
This study predicted the target genes of IPRN in the treatment of OP and preliminarily verified that IPRN plays an anti-OP role through the PI3K/AKT/mTOR pathway, which provides a new drug for the treatment of OP.
Association between inflammatory markers and bone mineral density: a cross-sectional study from NHANES 2007–2010
Authors: Chen Shuai , Sun Xiaohe , Jin Jie , Zhou Guowei , Li Zhiwei 
Published: April 2023

Abstract
Purpose
Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) are acknowledged as novel inflammatory markers. However, studies investigating the correlation between inflammatory markers and osteoporosis (OP) remain scarce. We aimed to investigate the relationship between NLR, MLR, PLR and bone mineral density (BMD).

Methods
A total of 9054 participants from the National Health and Nutrition Examination Survey were included in the study. MLR, NLR and PLR were calculated for each patient based on routine blood tests. Given the complex study design and sample weights, the relationship between inflammatory markers and BMD was evaluated through weighted multivariable-adjusted logistic regression and smooth curve fittings. In addition, several subgroup analyses were conducted to assess the robustness of the outcomes.

Results
This study observed no significant relationship between MLR and lumbar spine BMD (P = 0.604). However, NLR was positively correlated with lumbar spine BMD (β = 0.004, 95% CI: 0.001 to 0.006, P = 0.001) and PLR was negatively linked to lumbar spine BMD (β = − 0.001, 95% CI: − 0.001 to − 0.000, P = 0.002) after accounting for covariates. When bone density measurements were changed to the total femur and femoral neck, PLR was still significantly positively correlated with total femur (β = − 0.001, 95% CI: − 0.001, − 0.000, P = 0.001) and femoral neck BMD (β = − 0.001, 95% CI: − 0.002, − 0.001, P < 0.001). After converting PLR to a categorical variable (quartiles), participants in the highest PLR quartile had a 0.011/cm2 lower BMD than those in the lowest PLR quartile (β = − 0.011, 95% CI: − 0.019, − 0.004, P = 0.005). According to subgroup analyses stratified by gender and age, the negative correlation with PLR and lumbar spine BMD remained in males and age < 18 groups, but not in female and other age groups.

Conclusions
NLR and PLR were positively and negatively correlated with lumbar BMD, respectively. And PLR might serve as a potential inflammatory predictor of osteoporosis outperforming MLR and NLR. The complex correlation between the inflammation markers and bone metabolism requires further evaluation in large prospective studies.
Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann–Pick disease types A, B and A/B)
Authors: Geberhiwot Tarekegn , Wasserstein Melissa , Wanninayake Subadra , Bolton Shaun Christopher , Dardis Andrea , Lehman Anna , Lidove Olivier , Dawson Charlotte , Giugliani Roberto , Imrie Jackie , Hopkin Justin , Green James , de Vicente Corbeira Daniel , Madathil Shyam , Mengel Eugen , Ezgü Fatih , Pettazzoni Magali , Sjouke Barbara , Hollak Carla , Vanier Marie T. , McGovern Margaret , Schuchman Edward 
Published: April 2023

Abstract
Background
Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene. This rarity contributes to misdiagnosis, delayed diagnosis and barriers to good care. There are no published national or international consensus guidelines for the diagnosis and management of patients with ASMD. For these reasons, we have developed clinical guidelines that defines standard of care for ASMD patients.

Methods
The information contained in these guidelines was obtained through a systematic literature review and the experiences of the authors in their care of patients with ASMD. We adopted the Appraisal of Guidelines for Research and Evaluation (AGREE II) system as method of choice for the guideline development process.

Results
The clinical spectrum of ASMD, although a continuum, varies substantially with subtypes ranging from a fatal infantile neurovisceral disorder to an adult-onset chronic visceral disease. We produced 39 conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. In addition, these guidelines have identified knowledge gaps that must be filled by future research.

Conclusion
These guidelines can inform care providers, care funders, patients and their carers about best clinical practice and leads to a step change in the quality of care for patients with ASMD with or without enzyme replacement therapy (ERT).