bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regenerative endodontic procedures for two traumatized mature anterior teeth with transverse root fractures
Authors: Lu Jing , Kahler Bill 
Published: April 2022

Abstract
Background
Regenerative endodontic procedures (REPs) are an alternative treatment in immature traumatized teeth with necrotic pulp/apical periodontitis. However, this procedure has been infrequently reported in multiple transverse root fractures of mature teeth. This case report describes management of a patient with multiple horizontal root fractures in 2 maxillary central incisors that were successfully treated with REPs.

Case presentation
A 17-year-old girl had a history of traumatic injury to mature teeth 11 and tooth 21 resulting in multiple transverse root fractures. Clinical examination showed that both teeth responded to electric and thermal pulp sensibility tests with prolonged severe pain and were tender to percussion and palpation. Periapical radiographic examination showed both teeth were fully developed and had multiple transverse fractures in the mid-root. The pulp diagnosis was consistent with symptomatic irreversible pulpitis. REPs were initiated with only the coronal fragments treated to preserve pulp vitality in the apical fragment for potential pulp tissue regeneration. After REPs, clinical signs/symptoms subsided, and the two teeth were followed for 48 months when cone beam computed tomography (CBCT) imaging was also undertaken. At the last review, the case demonstrated root fractures healing with calcified tissue and pulp calcification in the apical fragments. Both teeth were stable and in function.

Conclusions
REPs have the potential to be used to treat traumatized and symptomatic mature permanent teeth that have sustained transverse root fractures.
Distinct gut and vaginal microbiota profile in women with recurrent implantation failure and unexplained infertility
Authors: Patel Nayna , Patel Nidhi , Pal Sejal , Nathani Neelam , Pandit Ramesh , Patel Molina , Patel Niket , Joshi Chaitanya , Parekh Bhavin 
Published: April 2022

AbstractBackgroundFemale reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women.MethodsWe recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31).ResultCompared with the controls, α-diversity and β-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05).Hungatella,associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genusLactobacillus,withLactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such asLeptotrichia and Snethia, occurred in the controls.ConclusionThe gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.
The predictive validity of admission criteria for the results of clinical competency assessment with an emphasis on family medicine in the fifth year of medical education: an observational study
Authors: Kötter Thomas , Rose Silvia Isabelle , Goetz Katja , Steinhäuser Jost 
Published: April 2022

Abstract
Background
In many countries, the number of applicants to medical schools exceeds the number of available places. This offers the need, as well as the opportunity to medical schools to select those applicants most suitable for later work as a doctor. However, there is no generally accepted definition of a ‘good doctor’. Clinical competencies may serve as surrogates. The aim of this study was to compare medical students in Germany selected based either on their pre-university grade point average alone or based on the result of a university-specific selection procedure regarding their clinical competencies with an emphasis on family medicine in the later years of training.

Methods
We used the ‘Allgemeinarztbarometer Ausbildung’ (Undergraduate Family Medicine Barometer), an instrument developed to assess clinical competencies with an emphasis on family medicine, to compare students in the pre-university grade point average admission-quota and the university-specific selection procedure admission-quota in the fifth year of training. Students were judged by their supervising general practitioners after a two-week practical course. Competencies were rated on a five-point Likert-scale (1 = ‘totally agree’ i.e. the student is very competent to 5 = ‘totally disagree’ i.e. the student is not competent at all).

Results
We included 94 students (66% female). Students in the university-specific selection procedure quota (n = 80) showed better mean scores in every item of the Undergraduate Family Medicine Barometer. We found a statistically significant difference between the two groups for the item assessing communication skills (M [university-specific selection procedure quota] = 1.81, SD = 0.84 vs. M [pu-GPA quota] = 2.38, SD = 0.96; t[91] = -2.23, p = .03; medium effect size). Logistic regression revealed no statistically significant age or gender contribution.

Conclusions
Despite the small sample-size, our results indicate, that students selected via an university-specific selection procedure show better communicative competencies in the later years of training.
Cysteine-rich protein 2 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm formation in mice
Authors: Chen Chung-Huang , Ho Hua-Hui , Jiang Wei-Cheng , Ao-Ieong Wai-Sam , Wang Jane , Orekhov Alexander N. , Sobenin Igor A. , Layne Matthew D. , Yet Shaw-Fang 
Published: April 2022

Abstract
Background
Abdominal aortic aneurysm (AAA) is a relatively common and often fatal condition. A major histopathological hallmark of AAA is the severe degeneration of aortic media with loss of vascular smooth muscle cells (VSMCs), which are the main source of extracellular matrix (ECM) proteins. VSMCs and ECM homeostasis are essential in maintaining structural integrity of the aorta. Cysteine-rich protein 2 (CRP2) is a VSMC-expressed protein; however, the role of CRP2 in AAA formation is unclear.

Methods
To investigate the function of CRP2 in AAA formation, mice deficient in Apoe (Apoe−/−) or both CRP2 (gene name Csrp2) and Apoe (Csrp2−/−Apoe−/−) were subjected to an angiotensin II (Ang II) infusion model of AAA formation. Aortas were harvested at different time points and histological analysis was performed. Primary VSMCs were generated from Apoe−/− and Csrp2−/−Apoe−/− mouse aortas for in vitro mechanistic studies.

Results
Loss of CRP2 attenuated Ang II-induced AAA incidence and severity, accompanied by preserved smooth muscle α-actin expression and reduced elastin degradation, matrix metalloproteinase 2 (MMP2) activity, deposition of collagen, particularly collagen III (Col III), aortic tensile strength, and blood pressure. CRP2 deficiency decreased the baseline MMP2 and Col III expression in VSMCs and mitigated Ang II-induced increases of MMP2 and Col III via blunting Erk1/2 signaling. Rescue experiments were performed by reintroducing CRP2 into Csrp2−/−Apoe−/− VSMCs restored Ang II-induced Erk1/2 activation, MMP2 expression and activity, and Col III levels.

Conclusions
Our results indicate that in response to Ang II stimulation, CRP2 deficiency maintains aortic VSMC density, ECM homeostasis, and structural integrity through Erk1/2–Col III and MMP2 axis and reduces AAA formation. Thus, targeting CRP2 provides a potential therapeutic strategy for AAA.
Prediction of programmed cell death protein 1 in hepatocellular carcinoma patients using radiomics analysis with radiofrequency-based ultrasound multifeature maps
Authors: Wang Qingmin , Dong Yi , Xiao Tianlei , Zhang Shiquan , Yu Jinhua , Li Leyin , Zhang Qi , Wang Yuanyuan , Xiao Yang , Wang Wenping 
Published: April 2022

AbstractBackgroundThis study explored the feasibility of radiofrequency (RF)-based radiomics analysis techniques for the preoperative prediction of programmed cell death protein 1 (PD-1) in patients with hepatocellular carcinoma (HCC).MethodsThe RF-based radiomics analysis method used ultrasound multifeature maps calculated from the RF signals of HCC patients, including direct energy attenuation (DEA) feature map, skewness of spectrum difference (SSD) feature map, and noncentrality parameter S of the Rician distribution (NRD) feature map. From each of the above ultrasound maps, 345 high-throughput radiomics features were extracted. Then, the useful radiomics features were selected by the sparse representation method and input into support vector machine (SVM) classifier for PD-1 prediction.Results and conclusionAmong all the RF-based prediction models and the ultrasound grayscale comparative model, the RF-based model using all of the three ultrasound feature maps had the highest prediction accuracy (ACC) and area under the curve (AUC), which were 92.5% and 94.23%, respectively. The method proposed in this paper is effective for the meaningful feature extraction of RF signals and can effectively predict PD-1 in patients with HCC.
Carbonic anhydrase IX-targeted H-APBC nanosystem combined with phototherapy facilitates the efficacy of PI3K/mTOR inhibitor and resists HIF-1α-dependent tumor hypoxia adaptation
Authors: Liu Jie , Hu Xiaochun , Feng Lei , Lin Yun , Liang Shujing , Zhu Zhounan , Shi Shuo , Dong Chunyan 
Published: April 2022

Abstract
Background
Non-redundant properties such as hypoxia and acidosis promote tumor metabolic adaptation and limit anti-cancer therapies. The key to the adaptation of tumor cells to hypoxia is the transcriptional and stable expression of hypoxia-inducible factor-1 alpha (HIF-1α). The phosphorylation-activated tumorigenic signal PI3K/AKT/mTOR advances the production of downstream HIF-1α to adapt to tumor hypoxia. Studies have elucidated that acid favors inhibition of mTOR signal. Nonetheless, carbonic anhydrase IX (CAIX), overexpressed on membranes of hypoxia tumor cells with pH-regulatory effects, attenuates intracellular acidity, which is unfavorable for mTOR inhibition. Herein, a drug delivery nanoplatform equipped with dual PI3K/mTOR inhibitor Dactolisib (NVP-BEZ235, BEZ235) and CAIX inhibitor 4‐(2‐aminoethyl) benzene sulfonamide (ABS) was designed to mitigate hypoxic adaptation and improve breast cancer treatment.

Results
ABS and PEG-NH2 were successfully modified on the surface of hollow polydopamine (HPDA), while BEZ235 and Chlorin e6 (Ce6) were effectively loaded with the interior of HPDA to form HPDA-ABS/PEG-BEZ235/Ce6 (H-APBC) nanoparticles. The release of BEZ235 from H-APBC in acid microenvironment could mitigate PI3K/mTOR signal and resist HIF-1α-dependent tumor hypoxia adaptation. More importantly, ABS modified on the surface of H-APBC could augment intracellular acids and enhances the mTOR inhibition. The nanoplatform combined with phototherapy inhibited orthotopic breast cancer growth while reducing spontaneous lung metastasis, angiogenesis, based on altering the microenvironment adapted to hypoxia and extracellular acidosis.

Conclusion
Taken together, compared with free BEZ235 and ABS, the nanoplatform exhibited remarkable anti-tumor efficiency, reduced hypoxia adaptation, mitigated off-tumor toxicity of BEZ235 and solved the limited bioavailability of BEZ235 caused by weak solubility.

Graphical Abstract
Engineering defected 2D Pd/H-TiO2 nanosonosensitizers for hypoxia alleviation and enhanced sono-chemodynamic cancer nanotherapy
Authors: Qiao Xiaohui , Xue Liyun , Huang Hui , Dai Xinyue , Chen Yu , Ding Hong 
Published: April 2022

Abstract
Background
Sonodynamic therapy (SDT) is a burgeoning modality for cancer therapy owing to its high tissue-penetrating capability, controllability and safety. Whereas, the undesirable reactive oxygen species (ROS) yield of sonosensitizers and tumor hypoxia are two vulnerable spots of SDT. Therefore, it is an advisable strategy to augment ROS level and simultaneously relieve hypoxia for SDT to arrive its full potential in cancer treatment.

Results
In this work, the defected two-dimensional (2D) Pd/H-TiO2 nanosheets (NSs) with triple antineoplastic properties were dexterously elaborated and engineered using a facile one-pot Pd-catalyzed hydrogenation tactic by loading a tiny amount of Pd and then inletting hydrogen flow at atmospheric pressure and temperature. The 2D black Pd/H-TiO2 NSs with oxygen defects exerted eximious SDT effect based on the decreased bandgap that made it easier for the separation of electrons and holes when triggered by ultrasound as theoretically guided by density functional theory calculations. Additionally, Pd/H-TiO2 NSs could serve as Fenton-like agents because of the presence of oxygen defects, facilitating the conversion of hydrogen peroxide into hydroxyl radicals for exerting the chemodynamic therapy (CDT). Simultaneously, the introduced tiny Pd component possessed catalase-like activity responsible for oxygen production to ameliorate hypoxic condition and thus contributed to improving SDT and CDT efficacies. Both in vitro and in vivo results provided compelling evidences of high ROS yield and aggrandized sono-chemodynamic effect of Pd/H-TiO2 nanosonosensitizers with the detailed underlying mechanism investigation by RNA sequencing.

Conclusion
This work delves the profound potential of Pd-catalyzed hydrogenated TiO2 on oncotherapy, and the effective antineoplastic performance and ignorable therapeutic toxicity make it a powerful competitor among a cornucopia of nanosonosensitizers.

Graphical Abstract
Integration of a community-based harm reduction program into a safety net hospital: a qualitative study
Authors: Khan Ghulam Karim , Harvey Leah , Johnson Samantha , Long Paul , Kimmel Simeon , Pierre Cassandra , Drainoni Mari-Lynn 
Published: April 2022

Abstract
Background
Community-based harm reduction programs reduce morbidity and mortality associated with drug use. While hospital-based inpatient addiction consult services can also improve outcomes for patients using drugs, inpatient clinical care is often focused on acute withdrawal and the medical management of substance use disorders. There has been limited exploration of the integration of community-based harm reduction programs into the hospital setting. We conducted a qualitative study to describe provider perspectives on the implementation of a harm reduction in-reach program.

Methods
We conducted 24 semi-structured interviews with providers from three different primary work sites within a safety net hospital in Boston, MA, in 2021. Interviews explored perceived facilitators and barriers to the implementation of the harm reduction in-reach program in the hospital setting and solicited recommendations for potential improvements to the harm reduction in-reach program. Interviews were analyzed using an inductive approach that incorporated principles of grounded theory methodology to identify prevailing themes.

Results
Twenty-four participants were interviewed from the harm reduction in-reach program, inpatient addiction consult service, and the hospital observation unit. Thematic analysis revealed seven major themes and multiple facilitators and barriers to the implementation of the harm reduction in-reach program. Participants highlighted the impact of power differences within the medical hierarchy on inter-team communication and clinical care, the persistence of addiction-related stigma, the importance of coordination and role delineation between care team members, and the benefits of a streamlined referral process.

Conclusions
Harm reduction programs offer accessible, patient-centered, low-barrier care to patients using drugs. The integration of community-based harm reduction programs into the inpatient setting is a unique opportunity to bridge inpatient and outpatient care and expand the provision of harm reduction services.
Trial registration: Not applicable.
The associations between interleukin-17 single-nucleotide polymorphism and colorectal cancer susceptibility: a systematic review and meta-analysis
Authors: Li Gaoming , Ma Jingfu , Zhang Ning , Li Xiaogang , Li Fangfang , Jiang Yuxing 
Published: April 2022

Abstract
Background
Numerous case-control studies have reported associations between interleukin-17 (IL-17) polymorphisms and colorectal cancer; however, the results were inconsistent. The aim of this meta-analysis was to further clarify the effects of IL-17 polymorphisms on colorectal cancer susceptibility.

Materials and method
Relevant studies were extracted from the electronic databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CMB) up to April 2021. The odds ratio and 95% confidence interval were used to estimate the strength of the associations.

Results
Ten articles including 2599 cases and 2845 controls were enrolled in our research after strict literature screening. Highly significant associations between the IL-17A rs2275913 polymorphism and increased colorectal cancer susceptibility were observed in all five gene models (allelic, dominant, recessive, homozygous, and heterozygous models), and subgroup analysis based on ethnicity revealed that these associations existed not only in the Asian population but also in the Caucasian population. However, the results showed no significantly elevated colorectal cancer risk correlated with the IL-17F rs763780 polymorphism, and a slightly lower colorectal cancer susceptibility for the Caucasian population was discovered in the recessive and homozygous models of this mutation.

Conclusion
The IL-17A rs2275913 polymorphism may be an independent risk factor contributing to colorectal cancer susceptibility, while the IL-17F rs763780 polymorphism may decrease susceptibility to colorectal cancer. Future studies with large-scale samples are warranted to identify these associations.
Risk factors for central venous catheter-associated deep venous thrombosis in pediatric critical care settings identified by fusion model
Authors: Li Haomin , Lu Yang , Zeng Xian , Feng Yuqing , Fu Cangcang , Duan Huilong , Shu Qiang , Zhu Jihua 
Published: April 2022

Abstract
Background
An increase in the incidence of central venous catheter (CVC)-related thrombosis (CRT) has been reported in pediatric intensive care patients over the past decade. Risk factors for the development of CRT are not well understood, especially in children. The study objective was to identify potential clinical risk factors associated with CRT with novel fusion machine learning models.

Methods
Patients aged 0–18 who were admitted to intensive care units from December 2015 to December 2018 and underwent at least one CVC placement were included. Two fusion model approaches (stacking and blending) were used to build a better performance model based on three widely used machine learning models (logistic regression, random forest and gradient boosting decision tree). High-impact risk factors were identified based on their contribution in both fusion artificial intelligence models.

Results
A total of 478 factors of 3871 patients and 3927 lines were used to build fusion models, one of which achieved quite satisfactory performance (AUC = 0.82, recall = 0.85, accuracy = 0.65) in 5-fold cross validation. A total of 11 risk factors were identified based on their independent contributions to the two fusion models. Some risk factors, such as D-dimer, thrombin time, blood acid-base balance-related factors, dehydrating agents, lymphocytes and basophils were identified or confirmed to play an important role in CRT in children.

Conclusions
The fusion model, which achieves better performance in CRT prediction, can better understand the risk factors for CRT and provide potential biomarkers and measures for thromboprophylaxis in pediatric intensive care settings.
Do German university medical centres promote robust and transparent research? A cross-sectional study of institutional policies
Authors: Holst M. R. , Faust A. , Strech D. 
Published: April 2022

Abstract
Background
In light of replication and translational failures, biomedical research practices have recently come under scrutiny. Experts have pointed out that the current incentive structures at research institutions do not sufficiently incentivise researchers to invest in robustness and transparency and instead incentivise them to optimize their fitness in the struggle for publications and grants. This cross-sectional study aimed to describe whether and how relevant policies of university medical centres in Germany support the robust and transparent conduct of research and how prevalent traditional metrics are.

Methods
For 38 German university medical centres, we searched for institutional policies for academic degrees and academic appointments as well as websites for their core facilities and research in general between December 2020 and February 2021. We screened the documents for mentions of indicators of robust and transparent research (study registration; reporting of results; sharing of research data, code and protocols; open access; and measures to increase robustness) and for mentions of more traditional metrics of career progression (number of publications; number and value of awarded grants; impact factors; and authorship order).

Results
While open access was mentioned in 16% of PhD regulations, other indicators of robust and transparent research were mentioned in less than 10% of institutional policies for academic degrees and academic appointments. These indicators were more frequently mentioned on the core facility and general research websites. Institutional policies for academic degrees and academic appointments had frequent mentions of traditional metrics.

Conclusions
References to robust and transparent research practices are, with a few exceptions, generally uncommon in institutional policies at German university medical centres, while traditional criteria for academic promotion and tenure still prevail.