bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of an elective ultrasound course for medical students
Authors: Kloth Christopher , Schmidt Stefan Andreas , Graeter Tilmann , Nikolaou Konstantin , Kaufmann Sascha , Beer Meinrad , Thaiss Wolfgang Maximilian
Published: February 2022

To evaluate the educational benefits of teaching ultrasound in an elective radiological course for medical students. We conducted a single‐center retrospective analysis of a one‐week elective ultrasound course in which 39 medical students (25 female; median age 25.8 ± 2.8 years, range 21–35, 4th and 5th years of undergraduate medical education) participated as part of their radiological training. The students completed a pre‐ and post‐course questionnaire using a five‐point Likert scale for self‐assessment of technical knowledge, confidence in the procedure regarding different organs, motivation for performing ultrasound, and the importance of ultrasound in medical education. The students also assessed the value of ultrasound teaching in the context of their general medical degree. Pre‐test and post‐test scores showed significantly improved radiology knowledge (p ≤ 0.001) concerning all abdominal organs (liver, spleen, gallbladder, kidney, urinary bladder, aorta and retroperitoneum). A significant improvement was registered in performing ultrasound of peripheral arteries and venous structures (each p = 0.001), and also of the thyroid gland (p = 0.006). General surveys at the end of the elective were overwhelmingly positive, with constructive criticism and complimentary comments. Systematic training in ultrasound markedly improved the students' skills. This was especially pronounced for solid organ structures, while students requested more education regarding the retroperitoneum and vascular structures. Teaching ultrasound in an elective hands‐on training course improves anatomical understanding and practical skills associated with increased motivation. The results affirm the necessity and clinical relevance of the course during the radiological training of medical students.
A novel LASSO‐derived prognostic model predicting survival for non‐small cell lung cancer patients with M1a diseases
Authors: Chen Hongchao , Huang Chen , Ge Huiqing , Chen Qianshun , Chen Jing , Li Yuqiang , Chen Haiyong , Luo Shiyin , Zhao Lilan , Xu Xunyu
Published: February 2022

Introduction

The current American Joint Committee on Cancer (AJCC) M1a staging of non‐small cell lung cancer (NSCLC) encompasses a wide disease spectrum, showing diverse prognosis.

Methods

Patients who diagnosed in an earlier period formed the training cohort, and those who diagnosed thereafter formed the validation cohort. Kaplan–Meier analysis was performed for the training cohort by dividing the M1a stage into three subgroups: (I) malignant pleural effusion (MPE) or malignant pericardial effusion (MPCE); (II) separate tumor nodules in contralateral lung (STCL); and (III) pleural tumor nodules on the ipsilateral lung (PTIL). Gender, age, histologic, N stage, grade, surgery for primary site, lymphadenectomy, M1a groups, and chemotherapy were selected as independent prognostic factors using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. And a nomogram was constructed using Cox hazard regression analysis. Accuracy and clinical practicability were separately tested by Harrell's concordance index, the receiver operating characteristic (ROC) curve, calibration plots, residual plot, the integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA).

Results

The concordance index (0.661 for the training cohort and 0.688 for the validation cohort) and the area under the ROC curve (training cohort: 0.709 for 1‐year and 0.727 for 2‐year OS prediction; validation cohort: 0.737 for 1‐year and 0.734 for 2‐year OS prediction) indicated satisfactory discriminative ability of the nomogram. Calibration curve and DCA presented great prognostic accuracy, and clinical applicability. Its prognostic accuracy preceded the AJCC staging with evaluated NRI (1‐year: 0.327; 2‐year: 0.302) and IDI (1‐year: 0.138; 2‐year: 0.130).

Conclusion

Our study established a nomogram for the prediction of 1‐ and 2‐year OS in patients with NSCLC diagnosed with stage M1a, facilitating healthcare workers to accurately evaluate the individual survival of M1a NSCLC patients. The accuracy and clinical applicability of this nomogram were validated.
Risk factors for venous thromboembolism in metastatic colorectal cancer with contemporary treatment: A SEER‐Medicare analysis
Authors: Ades Steven , Pulluri Bhargavi , Holmes Chris E. , Lal Inder , Kumar Santosh , Littenberg Benjamin
Published: February 2022

Background

The relationship between metastatic colorectal cancer (mCRC) and venous thromboembolism (VTE) is poorly defined in the modern era. Our objective was to examine impact of putative risk factors including newer treatments and anti‐angiogenic therapy on VTE incidence and survival in a modern older mCRC cohort.

Methods

This is a SEER‐Medicare cohort analysis of mCRC patients diagnosed in 2004–2009. Risk factor analysis was conducted using Cox models adjusted for sex, diagnosis age, race, primary tumor location, comorbidity, and prior VTE history, with cancer treatments as time‐varying covariates. Main outcomes were VTE incidence and overall survival.

Results

Ten thousand nine hundred and seventy six mCRC cases with mean age 77.9 years (range 65–107), 49.7% women, 83.5% white. There were 1306 VTE cases corresponding to 13.7% incidence at 1 year and 20.3% at 3 years. Independent VTE predictors included female sex (HR 1.27; 95% CI 1.14–1.42), African American race (HR 1.49; 1.27–1.73), prior VTE history (HR 16.3; 12.1–22.1), and right sided cancers (HR 1.16; 1.04–1.29). After adjustment, any therapy and bevacizumab (HR 0.68, 0.58–0.78) in particular were protective. Overall survival was 40.1% (39.4–41.3) at 1 year but improved significantly with any treatment. VTE following diagnosis of mCRC was associated with inferior OS (HR 1.09; 1.02–1.15).

Conclusions

In this large contemporary mCRC cohort, effective systemic therapy including anti‐angiogenic treatment was associated with lower VTE risk. Overall survival was poor, and modestly worse if a patient had a VTE at any time during treatment.
The outcome of watchful waiting in patients with previously treated follicular lymphoma
Authors: Fujino Takahiro , Maruyama Dai , Maeshima Akiko‐Miyagi , Saito Yo , Ida Hanae , Hosoba Rika , Yuda Sayako , Makita Shinichi , Fukuhara Suguru , Munakata Wataru , Suzuki Tatsuya , Kuroda Junya , Izutsu Koji
Published: February 2022

Watchful waiting (WW) is one of the standard approaches for newly diagnosed follicular lymphoma (FL) patients with low‐tumor burden. However, the impact of WW in FL patients at the first progression, remains unclear. We reviewed 206 FL patients who experienced the first progression after responding to the initial treatment at our institution between 1998 and 2017. Patients were classified into either the WW cohort (132 patients) or the immediate treatment cohort (74 patients). Overall, the median follow‐up from the first progression was 79.8 months (range, 2.1–227.0 months). In the WW cohort, the estimated median time to next treatment (TNT) was 19.7 months (95% confidence interval [CI], 13.4–30.2), and 76.5% (95% CI, 68.0–84.1) of the patients subsequently underwent the second‐line treatment at 5 years. There was a significant difference in the median time to treatment failure in the WW cohort (72.8 months; 95% CI, 64.6–94.0) compared to the immediate treatment cohort (23.3 months; 95% CI, 13.4–38.8) (HR, 2.13; 95% CI, 1.48–3.06), whereas overall survival and the cumulative incidence of histological transformation were not significantly different between two cohorts. In a multivariate analysis, rituximab refractory status, progression of disease within 24 months from the induction of first‐line therapy, and a high Follicular Lymphoma International Prognostic Index score at diagnosis were significantly associated with shorter TNT. Interestingly, 15 patients (11%) of the WW cohort experienced spontaneous tumor regression during WW, and their TNT (median, 82.1 months, 95% CI, 11.7‐NA) was longer than that of the remaining patients in the WW cohort (median, 16.5 months, 95% CI, 13.0–25.4), with a significant difference (p = 0.01). The results of the present study suggested that WW could be a safe and reasonable option even at the first progression for the selected FL patients, without a negative impact on clinical outcomes.
Relationship between protein structure and eating quality of rice under different nitrogen application rate
Authors: Liang Hanling , Gu Baiyu , Wang Tianyu , Rong Liyan , Sun Wentao , Wu Zhaoxia
Published: February 2022

Background and Objectives

The mechanisms underlying the effects of proteins on the eating quality of rice remain elusive. In this study, the effect of content and secondary structure of four rice proteins (glutelin, globulin, albumin, and prolamin) on eating quality was investigated with rice subjected to nitrogen treatment at 160, 210, 260, 315, and 420 kg N/ha in the field.

Findings

The results showed that applying nitrogen fertilizer remarkably increased glutelin and globulin contents (p < .05), especially the methionine content of globulin, leading to increased hardness of cooked rice. Moreover, excessive nitrogen significantly reduced the ratio of the prolamin α‐helix structure (p < .05), which had a significant correlation with hardness and pasting temperature (p < .05), at correlation coefficients of −0.859 and 0.828, respectively.

Conclusion

Besides protein content, the changes in amino acid content and protein secondary structure were also closely related to the eating quality of rice.

Significance and Novelty

Those results provided a new idea for breeding, cultivating, and processing technology regulation aimed at improving the eating quality of rice.
Uncommon manifestation of poisoning with a mixture of pesticides
Authors: Zoofaghari Shafeajafar , Namakizadeh Esfahani Navid , Akhavan Sigari Amirhossein , Tavakoli Nasim , Hashemzadeh Mozhdeh , Eizadi‐Mood Nastaran
Published: February 2022

The ingestion of pesticides for suicide commitment purposes is common in developing countries. We present a case of suicide with ingestion of mixed pesticides. The autopsy findings showed the presence of diazinon, chlorpyrifos, trifluralin, fenpropathrin, pyriproxyfen, and cypermethrin in his body. Clinicians managing poisoning cases need to be aware of poisoning with mixture of pesticides as a rare but highly fatal outcome.
Keratosis obturans: A rare cause of facial nerve palsy
Authors: Poudyal Prasanta , Nepal Gaurav , Yadav Sushil Kumar , Neupane Yogesh , Dutta Heempali , Pokhrel Shishir , Gaire Prabin
Published: February 2022

Keratosis obturans, caused by the deposition of desquamated keratin plug in the external auditory canal can present with facial palsy. Young patients presenting with facial palsy, earache, and gradual hearing loss should be suspected for Keratosis obturans.
Rare complication of a commonly used antihypertensive agent: A case of hydralazine‐induced ANCA‐associated vasculitis presenting as rapidly progressive glomerulonephritis
Authors: Warren Kayle , Vu Khiem , Shergill Karandeep , Watson Brian , Faris Mohamed
Published: February 2022

Hydralazine‐induced ANCA‐associated vasculitis is a rare clinical entity, with complications including rapidly progressive glomerulonephritis, pulmonary hemorrhage, and pulmonary‐renal syndrome. We present this case to highlight the clinical features that support this challenging diagnosis and to emphasize the importance of prompt recognition and aggressive intervention given its significant morbidity and mortality.
Reactive arthritis and silent thyroiditis following SARS‐CoV‐2 infection: Case report and review of the literature
Authors: Quaytman Jacob , Gollamudi Usha , Bass Noah , Suresh Shashank
Published: February 2022

SARS‐CoV‐2 has been implicated in the development of reactive arthritis (ReA) days to weeks following exposure or infection. We present a case of ReA with enthesitis and subsequent silent thyroiditis in a patient following infection with SARS‐CoV‐2, along with a review of the published cases of SARS‐CoV‐2‐related ReA.
Incorporation of Metal Active Sites on Porous Polycarbazoles for Photocatalytic CO2 Reduction
Authors: Wang Wenyan , Xi Yang , Yang Can , Byun Jeehye , Cheng Jiajia , Wang Sibo , Wang Xinchen
Published: February 2022

Photocatalytic conversion of carbon dioxide (CO2) to valuable products is one of the promising approaches to mitigate climate change and provide chemical fuels. The structural design of photocatalysts has been therefore directed to enhancing the CO2 conversion efficiency and selectivity. Herein, we report that the metalated porous polycarbazoles, made by facile one‐pot oxidative polymerization and successive transition metal impregnation, can effectively convert CO2 into carbon monoxide (CO) with high selectivity under visible light irradiation. The high porosity of the porous polycarbazoles provides enhanced CO2 adsorption and the incorporated metals facilitate the CO2 activation. The type of metal ions influences the CO selectivity by altering surface reaction kinetics for CO2 reduction. Our approach proves that the photocatalytic CO2 reduction ability and selectivity of porous conjugated polymers can be improved by decorating functional metal species to modulate the adsorption and activation behavior of CO2 molecules.
Induced Near‐Infrared Emission and Controlled Photooxidation based on Sulfonated Crown Ether in Water
Authors: Dong Xiaoyun , Zhang Cong , Dai Xianyin , Wang Qi , Zhang Ying‐Ming , Xu Xiufang , Liu Yu
Published: February 2022

Regulation of physio‐chemical properties and reaction activities via noncovalent methodology has become one of increasingly significant topics in supramolecular chemistry and showed inventive applications in miscellaneous fields. Herein, we demonstrate that sulfonated crown ether can form very stable host‐guest complexes with a series of push‐pull‐type photosensitizers, eventually leading to the dramatic fluorescence enhancement in visible and near‐infrared regions. Meanwhile, severe suppression in singlet oxygen (1O2) production is found, mainly due to the higher energy barriers between the excited single and triple states upon host‐guest complexation. Moreover, such complexation‐induced tuneable 1O2 generation systems has been utilized in adjusting the photochemical oxidation reactions of polycyclic aromatic hydrocarbons (anthracene) and sulfides ((methylthio)benzene) in water. This supramolecularly controlled photooxidation based on the selective molecular binding of crown ether with photosensitizers may provide a feasible and applicable strategy for monitoring and modulating many photocatalysis processes in aqueous phase.
Enantioselective synthesis of indole‐based unnaturalβ‐Alkynylα‐amino acid derivatives via chiral phosphoric acid catalysis
Authors: Woldegiorgis Alemayehu Gashaw , Gu Haorui , Lin Xufeng
Published: February 2022

The synthesis of unnaturalα‐amino acid derivatives has attracted considerable interest in recent years, as they are ubiquitous in protein synthesis and peptide‐based drug discovery. Herein, we reported the chiral phosphoric acid catalyzed asymmetric reaction of indoles withβ,γ‐alkynyl‐α‐imino esters for the enantioselective synthesis of unnatural indole‐basedα‐amino acid derivatives. This asymmetric organocatalysis protocol enables efficient synthesis of unnaturalα‐amino acid derivatives with a tetrasubstituted stereogenic center and an alkyne moiety with up to 99% yield and 98% ee, resulting in operationally simple conditions, short reaction time, and broad substrate scope.
Comparative effects of left bundle branch area pacing, His bundle pacing, biventricular pacing in patients requiring cardiac resynchronization therapy: A network meta‐analysis
Authors: Hua Juan , Wang Chenxi , Kong Qiling , Zhang Yichu , Wang Qijun , Xiong Ziyi , Hu Jinzhu , Li Juxiang , Chen Qi , Hong Kui
Published: February 2022

Background

The comparative effects of different types of cardiac resynchronization therapy (CRT) delivered by biventricular pacing (BVP), His bundle pacing (HBP), and left bundle branch area pacing (LBBAP) remain inconclusive.

Hypothesis

HBP and LBBAP may be advantageous over BVP for CRT.

Methods

PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for studies that reported the effects after BVP, HBP, and LBBAP for CRT. The effects between groups were compared by a frequentist random‐effects network meta‐analysis (NMA), by which the mean differences (MDs) and 95% confidence intervals (CIs) were calculated.

Results

Six articles involving 389 patients remained for the final meta‐analysis. The mean follow‐up of these studies was 8.03 ± 3.15 months. LBBAP resulted in a greater improvement in LVEF% (MD = 7.17, 95% CI = 4.31 to 10.04), followed by HBP (MD = 4.06, 95% CI = 1.09 to 7.03) compared with BVP. HBP resulted in a narrower QRS duration (MD = 31.58 ms, 95% CI = 12.75 to 50.40), followed by LBBAP (MD = 27.40 ms, 95% CI = 10.81 to 43.99) compared with BVP. No significant differences of changes in LVEF improvement and QRS narrowing were observed between LBBAP and HBP. The pacing threshold of LBBAP was significantly lower than those of BVP and HBP.

Conclusion

The NMA first found that LBBAP and HBP resulted in a greater LVEF improvement and a narrower QRS duration compared with BVP. Additionally, LBBAP resulted in similar clinical outcomes but with lower pacing thresholds, and may therefore offer advantages than does HBP for CRT.
Decreasing colorectal cancer screening disparities: A culturally tailored patient navigation program for Hispanic patients
Authors: Winkler Carl S. , Hardaway John C. , Ceyhan M. Erkan , Espat N. Joseph , Saied Calvino Abdul
Published: February 2022

Background

Colorectal cancer (CRC) is the second leading cause of cancer‐related death in Hispanic patients. Screening colonoscopy has been shown to reduce the incidence and mortality of CRC. However, utilization among Hispanic patients and other minority groups is low. The objective of this study was to evaluate colonoscopy utilization among Hispanic patients with a culturally tailored patient navigation program (CTPNP) in place.

Methods

A CTPNP was designed to meet the needs of the authors' Hispanic patient population and their health care system characteristics. A CTPNP protocol was created, and a Spanish‐speaking navigator/coordinator was hired. Enrolled patients received a Spanish‐language introductory letter, an initial phone call for patient education, and follow‐up calls to ensure that all potential barriers to colonoscopy were overcome. Colonoscopy completion (CC), colonoscopy cancellation (CN), and colonoscopy no‐show (NS) rates were recorded and compared with historical rates in Rhode Island.

Results

Over a 28‐month period, 773 patients were referred to the CTPNP, and 698 (53% female and 47% male) were enrolled in the program. The overall CC rate was 85% (n = 592) with no difference between males and females. The CN rate was 9% (n = 62), and the NS rate was 6% (n = 44). The most common reasons for CN and NS were cost and an inability to contact the patient after referral. Within the CC group, 43% (n = 254) of patients underwent polypectomy, and 1.3% (n = 8) required colectomy. Ninety percent (n = 530) of the CC group reported that they would not have completed colonoscopy without the CTPNP.

Conclusions

Implementation of a CTPNP is an effective intervention to improve the CC rate and eliminate the historical gender gap in utilization among Hispanic patients.
Tumor‐infiltrating lymphocytes in breast FNA biopsy cytology: A predictor of tumor‐infiltrating lymphocytes in histologic evaluation
Authors: Odate Toru , Le Minh‐Khang , Kawai Masataka , Kubota Mizuki , Yamaguchi Yohei , Kondo Tetsuo
Published: February 2022

Background

Tumor‐infiltrating lymphocytes (TILs) are associated with various clinicopathological features. Using cytologic specimens for assessing TILs remains to be established. This retrospective study aimed to establish a practical method to assess TILs in cytologic samples.

Methods

The authors found 1101 breast fine‐needle aspiration biopsy (FNAB) cytology samples in their hospital, and 214 of them met the inclusion criteria. The TILs score was evaluated using histologic slides, and breast cancers were divided into 2 groups: low‐ (<60%) and high‐TILs (≥60%). Training and validation tests composed of 50 breast cancer samples each were constructed. A cytologic TILs (cTILs) score was introduced to evaluate lymphocytes in FNAB cytology and it was compared with histologically evaluated TILs. The cTILs score was calculated by subtracting the number of neutrophils from the number of lymphocytes surrounding the tumor cells.

Results

In the training test, a 2‐tier system with low‐ and high‐TILs groups showed a large area under the curve (AUC) (0.943; 95% confidence interval [CI], 0.84‐0.99). A cTILs score cutoff value of >8 had 87.5% sensitivity and 90.5% specificity. In the validation test, the AUC was 0.79 (95% CI, 0.6‐0.93) whereas sensitivity and specificity were 57% and 89.5%, respectively. When small tumors <0.5 cm were excluded, the AUC improved to 0.93 (95% CI, 0.83‐1.0), and sensitivity and specificity were 80% and 88.5%, respectively.

Conclusions

The cTILs scoring system had acceptable reproducibility and concordance with TILs on histologic samples for tumors ≥0.5 cm. Cytologic evaluation can potentially substitute for histologic evaluation of TILs.
Synthesis and Optical Properties of Fluorinated Tetraphenylethylenes**
Authors: Zhang Zhenglin , Lieu Thien , Wang Xiqu , Daugulis Olafs , Miljanić Ognjen Š.
Published: February 2022

Four extensively fluorinated tetraphenylethylenes (TPE) and one extensively fluorinated triphenylethylene have been synthesized using combinations of copper‐catalyzed C−H functionalization reactions and Stille coupling reactions. Surprisingly, in contrast to the parent TPE, these compounds show little to no aggregation‐induced emission (AIE). Instead, photocyclization into fluorinated phenanthrene products occurs. Effects of solvent and oxygen on the yield and selectivity of this photocyclization have been examined.
An evolutionary computing‐based energy‐efficient solution for IoT‐enabled software‐defined sensor network architecture
Authors: Mishra Pooja , Kumar Neetesh , Godfrey W. Wilfred
Published: February 2022

Software‐defined networking (SDN) has emerged as an evolving technique in wireless sensor networks (WSNs). SDN enables WSNs with programmable control to manage network functions dynamically and efficiently. In Internet of Things (IoT) applications, smart sensors suffer from the low battery issue, generally deployed in harsh network environments where regular recharge is not feasible. Moreover, integrating SDN with IoT‐enabled sensor network puts forward several challenges, for example, control nodes' selection, load balancing, and energy cost optimization while aggregating the collected data, focusing on heterogeneous traffic data. Thus, an energy‐efficient data collection technique via definite sensing control in two‐level IoT‐enabled software‐defined heterogeneous WSN (2SD‐HWSN) is formulated as an optimization problem, with transmission distance from smart sensors, residual energy of sensors, and load based on node density. The proposed algorithm is divided into two: set‐up and transmission phases. In the set‐up phase, the control server (CS) elects the best‐suited control nodes (CNs) and sets up a schedule for coordinating data transmission. Further, normal nodes join appropriate CNs based on distance and residual energy. This way, CNs form clusters and route sensed data during the transmission phase. Therefore, an alternative nature‐inspired algorithm, that is, grey wolf optimization (GWO), is hybridized with particle swarm optimization using a low‐level co‐evolutionary technique to improve its overall performance. This hybrid variant of GWO, known as HGWO‐BC, offers balanced clustering (BC) via novel fitness function design. An exhaustive simulation study is performed in different scenarios considering homogeneous and heterogeneous sensors. Comparative results show that the HGWO‐BC outperforms state‐of‐the‐arts concerning network lifetime, instability period, residual energy, throughput, and computational efforts.
Depth‐limiting resistant layers restrict dimensions and positions of estuarine channels and bars
Authors: Pierik Harm Jan , Leuven Jasper R. F. W. , Busschers Freek S. , Hijma Marc P. , Kleinhans Maarten G.
Published: February 2022

Estuaries comprise channels vital for economic activity and bars as valuable habitats. They are increasingly under human‐induced pressures (e.g. sea‐level rise and dredging), resulting in morphological changes that affect navigability, flood safety and ecology. Antecedent geology may strongly steer how estuary channels will adapt to these pressures, but is surprisingly absent in most models. Here geological data and a unique bathymetry dataset covering 200 years from the Ems‐Dollard estuary (Netherlands/Germany) were used to demonstrate how local resistant layers force the position and dimensions of confluences and bars on the scale of an entire estuary. These layers limit channel depth and consequently cause widening, resulting in mid‐channel bar formation and increased channel curvature. This could lead to unexpected estuary widening and may cause land loss in densely populated areas. With increasing channel volume (as may happen again under future sea‐level rise), resistant layers in the estuary's substrate become more exposed, which enhances their effects. Many systems around the world contain shallow resistant layers that potentially constrain estuary channel dimensions and steer bank erosion. This highlights that resistant layer effects are important to consider as part of mixed depositional processes in coastal environments. It is therefore necessary to globally account for the effects of inherited resistant layers in the possible response of estuaries to sea‐level rise and increased tidal penetration.
Implementation of a marker substance for monitoring in situ 17‐keto modifications in endogenous steroids caused by microbiological contamination
Authors: Pfeffer Sandra , Gmeiner Günter , Gärtner Peter
Published: February 2022

The urinary steroid profile established for the monitoring of eventual testosterone or testosterone precursor application by athletes includes concentrations and ratios of various endogenously produced steroidal hormones and metabolites. Due to enzymatic activities in urine specimens, the concentrations of these endogenous steroids and consequently their ratios may alter, leading to potential misinterpretation of analytical results. Microbiological contamination in athletes' urine samples can occur due to urinary tract infections or due to contamination by the non‐sterile sample collection conditions. Depending on the duration of transportation of urine samples, the transport and storage conditions may favour microorganisms' growth, and therefore, the enzymatic activity can be accelerated. Degradation effects on endogenous steroids caused by microorganisms have been observed, such as hydrolysis of steroid conjugates, increase of testosterone in the free fraction or modification of the steroid structure by oxidoreductive reactions. The World Anti‐Doping Agency (WADA) implemented criteria to check for signs of microbial degradation in a technical document dealing with the detection, analysis and reporting of endogenous androgenic anabolic steroids (TD EAAS) in urine samples. During the endogenous steroid profile confirmation procedures (CPs) of the WADA accredited Seibersdorf Laboratory, significant differences in the concentrations of markers of the steroid profile were observed compared to the initial testing procedures (ITPs). The changes in concentrations of the urinary steroid profile were attributed to the reduction of the 17‐keto group to a 17β‐hydroxy group caused by increased enzymatic activity during the hydrolysis step. In order to monitor the 17‐keto reduction activity in athletes' urine specimens, possible marker substances containing a 17‐keto group were synthesised and added in the internal standards mixture (ISTD) of the ITP. The presence of the reduced 17β‐hydroxy form of the marker substance indicated enzymatic activity leading to 17‐keto reduction reactions. The substance 3β‐ethoxy‐5α‐androstane‐17‐one was defined to be suitable to indicate 17‐keto reduction reactions occurring during hydrolysis carried out at moderate temperatures.
Does effective population size affect rates of molecular evolution: Mitochondrial data for host/parasite species pairs in bees suggests not
Authors: Shokri Bousjein Nahid , Tierney Simon M. , Gardner Michael G. , Schwarz Michael P.
Published: February 2022

Adaptive evolutionary theory argues that organisms with larger effective population size (Ne) should have higher rates of adaptive evolution and therefore greater capacity to win evolutionary arm races. However, in some certain cases, species with much smaller Ne may be able to survive besides their opponents for an extensive evolutionary time. Neutral theory predicts that accelerated rates of molecular evolution in organisms with exceedingly small Ne are due to the effects of genetic drift and fixation of slightly deleterious mutations. We test this prediction in two obligate social parasite species and their respective host species from the bee tribe Allodapini. The parasites (genus Inquilina) have been locked into tight coevolutionary arm races with their exclusive hosts (genus Exoneura) for ~15 million years, even though Inquilina exhibit Ne that are an order of magnitude smaller than their host. In this study, we compared rates of molecular evolution between host and parasite using nonsynonymous to synonymous substitution rate ratios (dN/dS) of eleven mitochondrial protein‐coding genes sequenced from transcriptomes. Tests of selection on mitochondrial genes indicated no significant differences between host and parasite dN/dS, with evidence for purifying selection acting on all mitochondrial genes of host and parasite species. Several potential factors which could weaken the inverse relationship between Ne and rate of molecular evolution are discussed.
The repeated evolution of stripe patterns is correlated with body morphology in the adaptive radiations of East African cichlid fishes
Authors: Urban Sabine , Gerwin Jan , Hulsey C. Darrin , Meyer Axel , Kratochwil Claudius F.
Published: February 2022

Color patterns are often linked to the behavioral and morphological characteristics of an animal, contributing to the effectiveness of such patterns as antipredatory strategies. Species‐rich adaptive radiations, such as the freshwater fish family Cichlidae, provide an exciting opportunity to study trait correlations at a macroevolutionary scale. Cichlids are also well known for their diversity and repeated evolution of color patterns and body morphology. To study the evolutionary dynamics between color patterns and body morphology, we used an extensive dataset of 461 species. A phylogenetic supertree of these species shows that stripe patterns evolved ~70 times independently and were lost again ~30 times. Moreover, stripe patterns show strong signs of correlated evolution with body elongation, suggesting that the stripes’ effectiveness as antipredatory strategy might differ depending on the body shape. Using pedigree‐based analyses, we show that stripes and body elongation segregate independently, indicating that the two traits are not genetically linked. Their correlation in nature is therefore likely maintained by correlational selection. Lastly, by performing a mate preference assay using a striped CRISPR‐Cas9 mutant of a nonstriped species, we show that females do not differentiate between striped CRISPR mutant males and nonstriped wild‐type males, suggesting that these patterns might be less important for species recognition and mate choice. In summary, our study suggests that the massive rates of repeated evolution of stripe patterns are shaped by correlational selection with body elongation, but not by sexual selection.
Evolutionary analyses of visual opsin genes in frogs and toads: Diversity, duplication, and positive selection
Authors: Schott Ryan K. , Perez Leah , Kwiatkowski Matthew A. , Imhoff Vance , Gumm Jennifer M.
Published: February 2022

Among major vertebrate groups, anurans (frogs and toads) are understudied with regard to their visual systems, and little is known about variation among species that differ in ecology. We sampled North American anurans representing diverse evolutionary and life histories that likely possess visual systems adapted to meet different ecological needs. Using standard molecular techniques, visual opsin genes, which encode the protein component of visual pigments, were obtained from anuran retinas. Additionally, we extracted the visual opsins from publicly available genome and transcriptome assemblies, further increasing the phylogenetic and ecological diversity of our dataset to 33 species in total. We found that anurans consistently express four visual opsin genes (RH1, LWS, SWS1, and SWS2, but not RH2) even though reported photoreceptor complements vary widely among species. The proteins encoded by these genes showed considerable sequence variation among species, including at sites known to shift the spectral sensitivity of visual pigments in other vertebrates and had conserved substitutions that may be related to dim‐light adaptation. Using molecular evolutionary analyses of selection (dN/dS) we found significant evidence for positive selection at a subset of sites in the dim‐light rod opsin gene RH1 and the long wavelength sensitive cone opsin LWS. The function of sites inferred to be under positive selection are largely unknown, but a few are likely to affect spectral sensitivity and other visual pigment functions based on proximity to previously identified sites in other vertebrates. We also found the first evidence of visual opsin duplication in an amphibian with the duplication of the LWS gene in the African bullfrog, which had distinct LWS copies on the sex chromosomes suggesting the possibility of sex‐specific visual adaptation. Taken together, our results indicate that ecological factors, such as habitat and life history, as well as behavior, may be driving changes to anuran visual systems.
Shaping sustainable harvest boundaries for marine populations despite estimation bias
Authors: Goto Daisuke , Devine Jennifer A. , Umar Ibrahim , Fischer Simon H. , De Oliveira José A. A. , Howell Daniel , Jardim Ernesto , Mosqueira Iago , Ono Kotaro
Published: February 2022

Biased estimates of population status are a pervasive conservation problem. This problem has plagued assessments of commercial exploitation of marine species and can threaten the sustainability of both populations and fisheries. We develop a computer‐intensive approach to minimize adverse effects of persistent estimation bias in assessments by optimizing operational harvest measures (harvest control rules) with closed‐loop simulation of resource‐management feedback systems: management strategy evaluation. Using saithe (Pollachius virens), a bottom water, apex predator in the North Sea, as a real‐world case study, we illustrate the approach by first diagnosing robustness of the existing harvest control rule and then optimizing it through propagation of biases (overestimated stock abundance and underestimated fishing pressure) along with select process and observation uncertainties. Analyses showed that severe biases lead to overly optimistic catch limits and then progressively magnify the amplitude of catch fluctuation, thereby posing unacceptably high overharvest risks. Consistent performance of management strategies to conserve the resource can be achieved by developing more robust control rules. These rules explicitly account for estimation bias through a computational grid search for a set of control parameters (threshold abundance that triggers management action, Btrigger, and target exploitation rate, Ftarget) that maximize yield while keeping stock abundance above a precautionary level. When the biases become too severe, optimized control parameters—for saithe, raising Btrigger and lowering Ftarget—would safeguard against a overharvest risk (<3.5% probability of stock depletion) and provide short‐term stability in catch limit (<20% year‐to‐year variation), thereby minimizing disruption to fishing communities. The precautionary approach to fine‐tuning adaptive risk management through management strategy evaluation offers a powerful tool to better shape sustainable harvest boundaries for exploited resource populations when estimation bias persists. By explicitly accounting for emergent sources of uncertainty, our proposed approach ensures effective conservation and sustainable exploitation of living marine resources even under profound uncertainty.
The effectiveness of opportunistic public reports versus professional data to estimate large carnivore distribution
Authors: Gantchoff Mariela G. , Conlee Laura , L. Belant Jerrold
Published: February 2022

Species distribution models are key to spatially explicit conservation and management plans. Modeling distributions using data collected by the public has become increasingly popular; however, it is vital to evaluate their advantages and limitations. We investigated whether distribution models developed using opportunistic data (public reports) are congruent with those developed using professional data, while evaluating two strategies to remove spatial biases: data filtering and covariate removal. We compared GPS telemetry data (598 locations, 2010–2018) with public reports (1384 locations, 2016–2019) of American black bears (Ursus americanus) in Missouri (USA). Reports were subdivided into unfiltered reports, filtered reports (more reliable), and verified reports (confirmed by state agency staff). Each data set was modeled twice, with and without road covariates. Each distribution model was an ensemble of three machine‐learning methods. Models using filtered or verified reports and excluding road covariates were most similar to the telemetry model, both in spatial extent and spatial suitability patterns. However, the report‐derived distributions included several times more agriculture and developed land. The inclusion of roads resulted in spurious patterns and consistently reduced the predicted distribution area by ~10%. Elevation and vegetation productivity were consistently selected as the most important variables, regardless of data source and covariates included in models, but the report‐derived distributions included more agriculture and developed lands. Filtering data for reliability and removing covariates related to spatial biases resulted in models suitable to estimate broad black bear distribution, though differences remained that could represent different segments of the bear population (e.g., dispersing vs. established). Verification was not essential to develop suitable models if reports are filtered for reliability, important for areas that lack professionally collected data to model species distributions.
2H1C Mimicry: Bioinspired Iron and Zinc Complexes Supported by N,N,O Phenolate Ligands
Authors: Monkcom Emily C. , Negenman Hidde A. , Masferrer‐Rius Eduard , Lutz Martin , Ye Shengfa , Bill Eckhard , Klein Gebbink Robertus J. M.
Published: February 2022

In pursuit of mimicking the ubiquitous 2H1C motif in mononuclear non‐heme iron enzymes, two new bioinspired N,N,O phenolate ligands, BenzImNNO and ImPh2NNO, are synthesised and their coordination chemistry with zinc(II) and iron(II) is explored. BenzImNNO coordinates by means of an anionic κ3‐N,N,O donor set and readily forms homoleptic bisligated complexes, also in the presence of equimolar amounts of metal salt. In contrast, the increased steric bulk of ImPh2NNO promotes the formation of dinuclear complexes, [M2(ImPh2NNO)2(OTf)2] (M=Fe, Zn), with facially opposing metal sites, as a result of its unique bridging μ2:κ2‐N,N:κ1‐O coordination mode. We investigate the robustness of the ligand's dinucleating coordination mode during oxidative transformations and demonstrate that its coordination mode is retained upon triflate substitution for a biorelevant thiophenolate co‐ligand.
Metal‐free phthalimide‐labeled peptide nucleic acids for electrochemical biosensing applications
Authors: Magni Mirko , Dall'Angelo Sergio , Baldoli Clara , Licandro Emanuela , Falciola Luigi , Mussini Patrizia R.
Published: February 2022

Peptide nucleic acids (PNAs) are neutral mimics of natural DNA and RNA biopolymers that have caught the attention of researchers working on the identification of specific sequences of nucleobases in DNA/RNA strands. For this purpose, specific analytical protocols need to be developed to optimize the nucleic acid recognition ability of PNAs, exploiting both the high intrinsic affinity of PNA/DNA(RNA) couples as well as suitable markers, either linked to the PNA backbone or properly interacting with it in the working medium. In this context, the paper reports on phthalimide and 4‐nitrophthalimide as two cheap, metal‐free electroactive markers covalently bound to the pseudo‐peptide backbone of a PNA decamer. After a preliminary characterization of the markers, as such and in PNA conjugates, attention has been moved toward the optimization of the detectability of the labeled PNA decamers in aqueous solutions. Exploiting the potentiometric stripping analysis on hanging mercury drop electrode it has been possible to reach satisfactory detection limits of ca. 10 nM avoiding the use of expensive transition metal complexes as labels and/or of co‐reagents.
Identification of the promising olive (Olea europaea L.) cultivars based on morphological and pomological characters
Authors: Khadivi Ali , Mirheidari Farhad , Moradi Younes , Paryan Simin
Published: February 2022

Olive (Olea europaea L.) is an ancient tree and can tolerate drought very well. In the present study, morphological and pomological diversity of 24 olive cultivars (5–15 replications for each cultivar, 243 trees in total) was evaluated. There were significant differences among the cultivars studied based on the characters recorded. The CV was more than 20.00% in 46 of 50 characters measured. Leaf length ranged from 27.07 to 78.54 mm, and leaf width varied from 5.42 to 23.06 mm. Ripening date ranged from late‐August to early‐October. Fruit length ranged from 13.04 to 33.72 mm, fruit diameter varied from 10.24 to 23.71 mm, fruit weighted from 0.97 to 9.61 g, and the range of fruit flesh thickness was 1.63–7.65 mm. There was high variability in terms of fruit color, ranging from light green to black. Hierarchical cluster analysis (HCA) performed based on the mean of replications with Euclidean distance and Ward method grouped the cultivars into two major clusters. Differences in many of the morphological traits were observed across the cultivars. These sets of data were used to identify unique and desirable cultivars morphologically. The present research demonstrates that local olive cultivars have unique characteristics that differentiate them from imported cultivars. Thus, local cultivars provide novel genetic resources that should be conserved.
Machine learning directed sentinel lymph node biopsy in cutaneous head and neck melanoma
Authors: Oliver Jamie R. , Karadaghy Omar A. , Fassas Scott N. , Arambula Zack , Bur Andrés M.
Published: February 2022

Background

The specificity of sentinel lymph node biopsy (SLNB) for detecting lymph node metastasis in head and neck melanoma (HNM) is low under current National Comprehensive Cancer Network (NCCN) treatment guidelines.

Methods

Multiple machine learning (ML) algorithms were developed to identify HNM patients at very low risk of occult nodal metastasis using National Cancer Database (NCDB) data from 8466 clinically node negative HNM patients who underwent SLNB. SLNB performance under NCCN guidelines and ML algorithm recommendations was compared on independent test data from the NCDB (n = 2117) and an academic medical center (n = 96).

Results

The top‐performing ML algorithm (AUC = 0.734) recommendations obtained significantly higher specificity compared to the NCCN guidelines in both internal (25.8% vs. 11.3%, p < 0.001) and external test populations (30.1% vs. 7.1%, p < 0.001), while achieving sensitivity >97%.

Conclusion

Machine learning can identify clinically node negative HNM patients at very low risk of nodal metastasis, who may not benefit from SLNB.
Real‐world use of palbociclib monotherapy in retroperitoneal liposarcomas at a large volume sarcoma center
Authors: Nassif Elise F. , Cope Brandon , Traweek Raymond , Witt Russell G. , Erstad Derek J. , Scally Christopher P. , Thirasastr Prapassorn , Zarzour Maria Alejandra , Ludwig Joseph , Benjamin Robert , Bishop Andrew J. , Guadagnolo B. Ashleigh , Ingram Davis , Wani Khalida , Wang Wei‐Lien , Lazar Alexander J. , Torres Keila E. , Hunt Kelly K. , Feig Barry W. , Roland Christina L. , Somaiah Neeta , Keung Emily Z.
Published: February 2022

Palbociclib has been evaluated in early phase trials for well‐differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) patients, with reported median progression‐free survival (PFS) of 18 weeks. Here, we report on real‐world use and surgical outcomes associated with palbociclib treatment. We retrospectively reviewed 61 consecutive patients with retroperitoneal WDLPS (n = 14) or DDLPS (n = 47) treated with palbociclib monotherapy between 1 March 2016 and 28 February 2021 at The University of Texas MD Anderson Cancer Center. At palbociclib initiation, median age was 64 (interquartile range [IQR] 56‐72). In WDLPS and DDLPS cohorts, the median number of prior systemic treatments was 0 (IQR 0‐0) and 2 (IQR 0‐4), respectively. Median number of prior surgeries was 2 (WDLPS IQR 1‐2.75) and 2 (DDLPS IQR 1‐3). Median PFS was 9.2 (WDLPS IQR 3.9‐21.9) and 2.6 months (DDLPS IQR 2.0‐6.1), with median time on treatment of 7.4 months (WDLPS IQR 3.5‐14.2) and 2.7 months (DDLPS IQR 2.0‐5.7). Twelve patients ultimately underwent surgical resection. Resections were macroscopically complete (R0/R1) in half (n = 6/12), among whom only one patient experienced relapse after resection (median follow‐up 7.5 months). All patients who underwent macroscopically incomplete resections progressed after surgery with median time to progression of 3.3 months (IQR 2.3‐4.4). Surgery after palbociclib treatment was not associated with improved overall survival. Efficacy of palbociclib monotherapy for patients with advanced WDLPS and DDLPS is disappointing. While palbociclib may have been used to delay surgery, there was no clear benefit from treatment and few patients achieved prolonged tumor control.
Apelin‐13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin‐1/P2X7 axis and FAM134B‐dependent reticulophagy
Authors: Yang Yiyuan , Zhang Kai , Huang Shifang , Chen Wei , Mao Hui , Ouyang Xueqian , Chen Linxi , Li Lanfang
Published: February 2022

Cardiac hypertrophy is a leading cause of cardiac morbidity and mortality worldwide. Apelin is the endogenous ligand for the G protein‐coupled receptor, APJ. Previously, we have revealed that apelin‐13 can induce cardiomyocyte hypertrophy by activating the autophagy pathway. However, the precise mechanism through which apelin‐13 regulates reticulophagy to participate in cardiomyocyte hypertrophy remains unclear. Herein, we observed that apelin‐13‐induced cardiomyocyte hypertrophy by activating FAM134B‐dependent reticulophagy via the Pannexin‐1/P2X7 signal pathway. Furthermore, we found that apelin‐13 stimulated the opening of Pannexin‐1 hemichannel and increased extracellular ATP (eATP) levels, which activated the P2X7 purinergic receptor. Activation of the Pannexin‐1/eATP/P2X7 axis subsequently led to FAM134B‐dependent reticulophagy. Moreover, inhibition of the Pannexin‐1/P2X7 axis and FAM134B‐dependent reticulophagy reversed apelin‐13‐induced cardiomyocyte hypertrophy. Based on our present findings, apelin‐13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin‐1/P2X7 axis and FAM134B‐dependent reticulophagy.