bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of patient‐derived tumor organoid platform to predict the benefit of postoperative adjuvant chemotherapy for poor responders to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
Authors: Xue Weisong , Wang Ting , Yao Jiaxin , Wu Wei , Chen Dexin , Yan Botao , Dong Xiaoyu , Tang Yuting , Zeng Yunli , He Yueyu , Cao Peihua , Shao Fangyuan , Huang Wenhua , Deng Chuxia , Yan Jun 
Published: August 2023

AbstractPostoperative adjuvant chemotherapy (AC) for poor responders to neoadjuvant chemoradiotherapy (nCRT) remains debatable among patients with locally advanced rectal cancer (LARC), necessitating biomarkers to accurately predict the benefits of AC. This study aimed to develop a patient‐derived tumor organoid (PDTO) platform to predict the benefit of AC in LARC patients showing poor nCRT response. PDTOs were established using irradiated rectal cancer specimens with poor nCRT responses, and their sensitivity to chemotherapy regimens was tested. The half‐maximal inhibitory concentration (IC50) value for the PDTO drug test was defined based on the clinical outcomes, and the accuracy of the PDTO prognostic predictions was calculated. Predictive models were developed and validated using the PDTO drug test results. Between October 2018 and December 2021, 86 PDTOs were successfully constructed from 138 specimens (success rate 62.3%). The optimal IC50 cut‐off value for the organoid drug test was 39.31 μmol/L, with a sensitivity of 84.75%, a specificity of 85.19%, and an accuracy of 84.88%. Multivariate Cox regression analysis revealed that the PDTO drug test was an independent predictor of prognosis. A nomogram based on the PDTO drug test was developed, showing good prognostic ability in predicting the 2‐year and 3‐year disease‐free survivals (AUC of 0.826 [95% CI, 0.721–0.931] and 0.902 [95% CI, 0.823–0.982], respectively) and overall survivals (AUC of 0.859 [95% CI, 0.745–0.973] and 0.885 [95% CI, 0.792–0.978], respectively). The PDTO drug test can predict the benefit of postoperative AC in poor responders with LARC to nCRT.
Sternal foramina: An imaging study
Authors: Ma De‐Ting , Wang Jun‐Xia , Wang Zhao‐Hua , Cui Xue 
Published: August 2023

AbstractTo investigate the computed tomography (CT) image characteristics, adjacent tissues, and related measurement indices of the sternal foramina and provide an anatomical basis for the safety of minimally invasive sternum surgery. The data from 2500 thoracic multi‐slice computed tomography (MSCT) cases from January 2020 to June 2021 were analyzed retrospectively. The number and location of the sternal foramina and adjacent tissues (mediastinal adipose tissue, lung, pericardium) were observed. The size of the sternal foramina, CT value of the tissue inside the foramina, subcutaneous adipose tissue thickness, distance from skin to lung, distance from skin to the pericardium, and manubrio‐foraminal distance were measured. Sex differences were compared for each indicator performed. The incidence of sternal foramina was 4.44% (111/2500), with 83 males and 28 females. All sternal foramina were located at the mesosternum's fourth to sixth costal cartilage level. The transverse diameter of the sternal foramina was (0.60 ± 0.29) cm, and the vertical diameter was (0.68 ± 0.39) cm, which was greater in males than females (p > 0.01). The CT value of the tissue in the sternal foramina was (−77.05 ± 32.26) Hu, and there was no statistical difference between male and female patients (t = −1.780, p = 0.078). The adjacent tissues of the sternal foramina were only adjacent to adipose tissue in 41 cases (36.94%), pericardium in 18 patients (16.22%), lung tissue in 37 cases (33.33%), and both kinds of tissue in 15 cases (13.51%). The sternal foramina were not adjacent to the left lung in the female patients. In the sternal foramina region, the thickness of subcutaneous adipose tissue was (1.13 ± 0.51) cm, the distance from skin to lung was (1.86 ± 0.57) cm, the distance from skin to pericardium was (3.07 ± 0.72) cm, the manubrio‐foraminal distance was (12.68 ± 1.31) cm, which was significantly greater in males than in females (p < 0.05). The sternal foramina are closely related to the heart and lungs. The size and location of sternal foramina, the thickness of subcutaneous adipose tissue, and the distance from skin to heart and lung are all crucial factors in evaluating the safety of sternal puncture biopsy.
Accuracy analysis of traditional acupoint location and the coincidence of cutaneous arterial perforators and acupoints
Authors: Guo Chunxia , Zhang Yongguang , Ding Zhiwei , Han Rong , Jiao Xuwen , Hu Jinlian 
Published: August 2023

AbstractSeveral reports have shown a coincidence relationship between perforators and acupoints. However, there have been few previous reports of objective experimental methods to verify the reliability of the accuracy of acupoint location (APL) with nearby perforators. This research aimed to determine the internal agreement of the APL of five acupuncturists and to analyze the coincidence rate of acupoints with nearby perforators. Three two healthy volunteers were recruited with the inclusion and exclusion criteria. Three TCM clinical physicians determined acupoints in areas of the lower limb of participants. Two microsurgeons sketched corresponding regions based on the most common skin flap operation sites, located bone markers, and drew the skin flap axis. Doppler ultrasound was used to mark the perforator point and the distances measured for both points. There is no significant difference in the distance between the acupoints and perforators localization in different groups, and there are significant differences between the angle formed by acupoints and penetrators in all groups. All the points located by the traditional Chinese medicine (TCM) therapists are distributed around the dot. The distance between the coordinate point (A‐B) of 溫溜 Wēnliū (LI7) localization is the largest, reaching 16.6 mm. The accuracy of the acupoint location of each physician is limited by the clinical experience of physicians, and the difference among them is significant. There is a certain correspondence between the location of acupoints and perforators, which needs further studies to confirm.
The efficacy and safety of immune checkpoint inhibitors for patients with EGFR‐mutated non‐small cell lung cancer who progressed on EGFR tyrosine‐kinase inhibitor therapy: A systematic review and network meta‐analysis
Authors: Wang Zhen , Zhou Fang , Xu Shan , Wang Kang , Ding Huan 
Published: August 2023

AbstractBackgroundNon‐small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)‐mutated who progressed on EGFR tyrosine‐kinase inhibitor (EGFR‐TKI) therapy have limited therapeutic options. There is still no consensus on the role of immune checkpoint inhibitors (ICIs) in NSCLC with EGFR mutations.MethodsWe did a network meta‐analysis (NMA) with a systematic literature search on PubMed, Embase, Web of Science, and The Cochrane Library. We included all phase II and III randomized controlled trials (RCTs), non‐randomized controlled trials (Non‐RCTs), and retrospective studies. Progression‐free survival (PFS) and overall survival (OS) were assessed through hazard ratios (HR). Objective response rate (ORR) and adverse events (AEs) were assessed through odds ratio (OR) and relative risk (RR), respectively. R software was used to compare the outcomes of different treatments by Bayesian NMA.FindingsWe identified 1835 published results and 17 studies were included ultimately. A total of 2085 patients were included and accepted the following six treatments: ICIs plus chemotherapy (ICIs+Chemo), chemotherapy (Chemo), ICIs monotherapy (ICIs), ICIs plus chemotherapy and antiangiogenic therapy (ICIs+Chemo+Antiangio), antiangiogenic therapy plus chemotherapy (Antiangio+Chemo), ICIs plus antiangiogenic therapy (ICIs+Antiangio). ICIs+Chemo+Antiangio was associated with longer PFS and OS, as well as higher ORR (surface under the cumulative ranking curve [SUCRA], 96%, 90%, 91%). ICIs conferred the safety profile in terms of any‐grade AEs, grade greater than or equal to 3 AEs and any grade leading to treatment discontinuation occurred AEs (SUCRA, 99%, 68%, 94%).InterpretationICIs+Chemo+Antiangio brings the greatest survival benefit in NSCLC patients with EGFR mutations who progressed on EGFR‐TKI therapy, even for whom with baseline brain metastases. Compared with chemotherapy, ICIs has a low incidence of AEs and a benefit in OS.
Phytochemical Profiling by UPLC‐ESI‐QTOF‐MS of Kalaharia uncinata (Schinz) Moldenke, Widely Used in Traditional Medicine in DR Congo
Authors: Kibungu Kembelo Pathy , Tuenter Emmy , Vanhove Wouter , Belesi Katula Honoré , Van Damme Patrick , Pieters Luc 
Published: August 2023

AbstractKalaharia uncinata (Schinz) Moldenke, is a tropical erect bushy shrub or subshrub of the Lamiaceae family. It is an endemic plant species of Southern Africa, widely used in the pharmacopoeia against upper respiratory tract infections. A previously conducted ethnobotanical survey revealed that it is believed to contain bioactive substances. However, no relevant phytochemical information was available. This study aimed to perform a phytochemical characterization of K. uncinata and also to discuss the potential bioactivity of the identified phytochemical constituents based on documented data. Ultra‐performance liquid chromatography with electrospray ionization quadrupole time‐of‐flight mass spectrometry (UPLC‐ESI‐QTOF‐MS) was used for profiling and identification of the main phytochemical constituents from leaf extracts (MeOH 90 %, DCM, AcOEt, BuOH, hexane and residue) of K.uncinata. Twenty‐four constituents, representing mainly flavonoids (14), followed by phenylethanoid glycosides (7), phenolic acids (2), and an iridoid glycoside (1) were tentatively identified. Most of the identified compounds are documented to have antiviral and anti‐inflammatory properties, which could possibly be the rationale behind the use of K. uncinata against upper respiratory tract infections.
Nickel‐Catalyzed Cross‐Electrophile Coupling of Triazine Esters with Aryl Bromides
Authors: Liu Xiang , He Cai‐Yu , Yin Hao‐Nan , Miao Chengping , Chu Xue‐Qiang , Rao Weidong , Xu Hao , Zhou Xiaocong , Shen Zhi‐Liang 
Published: August 2023

Comprehensive SummaryCross‐electrophile coupling of triazine esters with aryl bromides could be facilely accomplished by employing nickel as catalyst, magnesium as metal mediator, and lithium chloride as additive. The reactions proceeded efficiently in THF at room temperature through C—O bond activation to afford an array of structurally different diaryl ketones in moderate to good yields with wide functional group tolerance. Control experiments showed that nickel, magnesium, lithium chloride, and THF are all indispensable for the good performance of the coupling reaction. Preliminary mechanistic exploration indicated that in situ formed arylmagnesium reagent by the insertion of magnesium into aryl bromide might serve as the key intermediate of the cross‐coupling. The method which avoids the utilization of moisture‐labile and relatively difficult‐to‐obtain organometallics is step‐economical, cost‐efficient, and operationally simple, potentially serving as an attractive alternative to documented methods.
Perspectives of patients undergoing neoadjuvant chemotherapy for breast cancer during the COVID‐19 pandemic
Authors: Gaughan Alice A. , MacEwan Sarah R. , Rush Laura J. , Gatti‐Mays Margaret E. , Pariser Ashley C. , McAlearney Ann Scheck 
Published: August 2023

AbstractBackgroundThe COVID‐19 pandemic resulted in a lapse in routine health care and cancer screenings for many individuals. This study sought to improve our understanding of the impact of the COVID‐19 pandemic on women being treated for breast cancer, both in general, and specifically related to their diagnosis.MethodsSemi‐structured interviews were conducted between August 2021 and February 2022 with women who were receiving neoadjuvant chemotherapy for early‐stage breast cancer at the Stefanie Spielman Comprehensive Breast Center in Columbus, Ohio. Interviews were recorded and transcribed verbatim. Transcripts were coded using deductive dominant thematic analysis and inductive coding that allowed for categorization of data as well as identification of emergent themes.ResultsData collected from our 19 interviews revealed that the COVID‐19 pandemic posed important challenges for breast cancer patients including fear of COVID‐19 infection and feelings of isolation. Most interviewees noted they had been vaccinated against COVID‐19 because of a desire to protect themselves and others from getting sick. Some women also expressed concerns about having delayed their screening mammograms due to the pandemic. Several patients described unexpected positive aspects of the pandemic such as being able to spend more time with family and having the ability to continue working because of the option to work from home during their cancer treatment.ConclusionsOur findings provide important insight about the impact of COVID‐19 on breast cancer patients. We highlight the positives that have been reported because of the pandemic, as well as the need to address delayed breast cancer screening.
Systematic Sampling of the Female Reproductive System for Molecular Characterization
Authors: Fisher Stephen A. , Grijalva Marielena , Guo Rong , Johnston Sarah A. , Laurent Louise C. , Nguyen Hieu , Renz John , Rosario Jean G. , Rudich Steven , Gregory Brian D. , Kim Junhyong , O'Neill Kathleen 
Published: August 2023

AbstractAs part of the National Institutes of Health Human BioMolecular Atlas Program to develop a global platform to map the 37 trillion cells in the adult human body, we are generating a comprehensive molecular characterization of the female reproductive system. Data gathered from multiple single‐cell/single‐nucleus and spatial molecular assays will be used to build a 3D molecular atlas. Herein, we describe our multistep protocol, beginning with an optimized organ procurement workflow that maintains functional characteristics of the uterus, ovaries, and fallopian tubes by perfusing these organs with preservation solution. We have also developed a structured tissue sampling procedure that retains information on individual‐level anatomic, physiologic, and individual diversity of the female reproductive system, toward full exploration of the function and structure of female reproductive cells. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Preparation and preservation of the female reproductive system (ovaries, fallopian tubes, and uterus) prior to procurementBasic Protocol 2: Removal of the female reproductive system en blocBasic Protocol 3: Postsurgical dissection of ovariesBasic Protocol 4: Postsurgical dissection of fallopian tubesBasic Protocol 5: Postsurgical dissection of cervixBasic Protocol 6: Postsurgical dissection of uterine bodySupport Protocol 1: OCT‐embedded tissue protocolSupport Protocol 2: Tissue fixation protocolSupport Protocol 3: Snap‐frozen tissue protocolBasic Protocol 7: Tissue slice preparation for Visium analysisSupport Protocol 4: Hematoxylin and eosin staining for 10X Visium imagingBasic Protocol 8: Manual tissue dissociation for Multiome analysisBasic Protocol 9: Tissue dissociation for Multiome analysis using S2 Singulator
Physiological contributors to yield in advanced cotton breeding lines
Authors: Virk Gurpreet , Snider John L. , Chee Peng , Virk Simerjeet , Parkash Ved , Kaur Navneet , Jones Donald 
Published: August 2023

AbstractCotton (Gossypium hirsutumL.) yield can be expressed as the product of intercepted photosynthetically active radiation (IPAR), radiation use efficiency (RUE), and harvest index (HI). Studies comparing genetic diversity in functional yield drivers for the progeny of elite breeding lines are limited or non‐existent. A field study was conducted during the 2020 and 2021 growing seasons to characterize crop development and to evaluate yield and underlying yield drivers in 16 advanced breeding lines (F7generation). Significant breeding line differences existed for lint yield, cutout date, reproductive, vegetative, and total biomass, RUE, and HI but not for IPAR. The lint yield for the lowest yielding lines was 24% lower than the highest yielding line with a lint yield of 1706 kg ha−1. Differences in RUE were not associated with single‐leaf photosynthetic rates. HI positively contributed to lint yield gain for most lines evaluated, whereas RUE was negatively correlated with lint yield for the majority of breeding lines evaluated. However, in the two highest‐yielding lines, two different strategies of yield maximization were identified. One line exhibited the earliest cutout date, reduced biomass production, low RUE, and the highest HI values, whereas the other line had the latest cutout date and produced the highest total biomass, highest RUE, and a low to intermediate HI. Breeding lines used in the current study achieved high yields by differentially manipulating underlying physiological components such as RUE, biomass accumulation, or dry matter allocation to fiber. Our work provides future direction for efforts aimed at maximizing yield through the selection for functional yield drivers.
Unraveling the dangerous duet between cancer cell plasticity and drug resistance
Authors: Chatterjee Namrata , Pulipaka Bhavana , Subbalakshmi Ayalur Raghu , Jolly Mohit Kumar , Nair Radhika 
Published: August 2023

AbstractCancer cell plasticity is the ability of tumor cells to switch phenotypes and is one of the predominant requisites of cancer cells capable of undergoing metastasis. Cancer cell plasticity is also recognized as one of the major contributors to intratumoral heterogeneity, a critical factor underlying the progression of malignant tumors, which is known to modify tumor response and induce resistance against various modes of therapy, thus posing a barrier to efficient cancer management. Cancer cell plasticity is acquired by the subversion of cell signaling pathways like mitogen‐activated protein kinase pathway, phosphoinositide‐3‐kinase, signal transducer and activator of transcription 3, Wnt, Hedgehog and Notch as well as cellular programs such as epithelial to mesenchymal transition and phenotypic plasticity. This complex phenomenon has been studied in many cancer types like pancreatic cancer, colon cancer and breast cancer. This review will explore the current understanding we have in breast cancer on the intrinsic molecular mechanisms of cancer cell plasticity and the resistance to various types of cancer therapy that arise as a result of plasticity. We conclude by exploring the potential novel therapies that specifically target the pathways leading to plasticity and can be leveraged to treat patients living with the disease.
A new high voltage gain DC‐DC converter based on active switched‐inductor technique
Authors: Imanlou Arash , Seifi Najmi Ebrahim , Babaei Ebrahim 
Published: August 2023

SummaryThis article proposes a brand‐new high voltage gain step‐up DC‐DC converter through the amalgamation of active switched‐inductors (A‐SL) and a coupled‐inductor (CL) unit. This topology stands out due to its capacity to achieve noteworthy high voltage amplification employing a lesser amount of components when put in contrast to other comparable topologies. The voltage stress across the switches is low, which enables the utilization of low‐voltage rating switches to elevate efficiency. Moreover, the division of the input current between the switches of the converter enables the power dissipation to be diminished. The CL is utilized in a way that if the turn ratio of its windings is lessened, the voltage boost will be augmented. Furthermore, the leakage energy is recycled through the output diode; therefore, problems such as voltage spikes across the switches do not occur. Moreover, the output diode turns off naturally without reverse recovery problems. The switching pattern of the converter is simple, and both switches are driven simultaneously, and the converter can be controlled using a simple controller in a closed‐loop control method. In addition, the duty cycle range has no limitations. The operation principle and the steady‐state analysis of the proffered converter are discussed in detail for CCM and DCM. The design considerations and efficiency analysis are provided, followed by small‐signal modeling and controller design. Moreover, to evaluate the performance of the proffered converter among other topologies, a comparison study is conducted in terms of voltage gain, total device count, and voltage tension on the power switches and diodes. Finally, a 200–300 W, 28/400 V lab‐based prototype is implemented and tested to validate the analysis.
Allosteric modulation of SHP2: Quest from known to unknown
Authors: Wang Ning , Zhu Shilin , Lv Dan , Wang Yajun , Khawar Muhammad B. , Sun Haibo 
Published: August 2023

AbstractSrc homology‐2 domain‐containing protein tyrosine phosphatase‐2 (SHP2) is a key regulatory factor in the cell cycle and its activating mutations play an important role in the development of various cancers, making it an important target for antitumor drugs. Due to the highly conserved amino acid sequence and positively charged nature of the active site of SHP2, it is difficult to discover inhibitors with high affinity for the catalytic site of SHP2 and sufficient cell permeability, making it considered an “undruggable” target. However, the discovery of allosteric regulation mechanisms provides new opportunities for transforming undruggable targets into druggable ones. Given the limitations of orthosteric inhibitors, SHP2 allosteric inhibitors have become a more selective and safer research direction. In this review, we elucidate the oncogenic mechanism of SHP2 and summarize the discovery methods of SHP2 allosteric inhibitors, providing new strategies for the design and improvement of SHP2 allosteric inhibitors.
Efficacy, safety, and tolerability of nivasorexant in adults with binge‐eating disorder: A randomized, Phase II proof of concept trial
Authors: McElroy Susan L. , Coloma Preciosa M. , Berger Benjamin , Guerdjikova Anna I. , Joyce J. Mark , Liebowitz Michael R. , Pain Scott , Rabasa Cristina 
Published: August 2023

AbstractObjectiveThis Phase II, placebo‐controlled, double‐blind study investigated the efficacy, safety, and tolerability of nivasorexant in the treatment of adults with moderate to severe binge‐eating disorder (BED).MethodsAdults meeting the DSM‐5 BED criteria were randomized 1:1 to placebo or nivasorexant (100 mg b.i.d.). The primary endpoint was the change from baseline to Week 12 in the number of binge eating (BE) days per week. Exploratory efficacy endpoints included cessation of BE in the last 4 weeks of treatment; and change from baseline to Week 12 in the number of BE episodes/week, the clinician global impression (CGI) of change, the Yale‐Brown Obsessive‐Compulsive Scale modified for BE, and the Hamilton rating scale for depression (HAMD‐17). Key safety outcomes included treatment‐emergent adverse events (TEAEs) and adverse events of special interest (i.e., somnolence and fatigue).ResultsSixty‐eight participants were randomized to each treatment arm. The change from baseline to Week 12 in the number of BE days/week was the same for placebo (least squares mean [LSM]: −2.93) and nivasorexant (LSM: −2.93), with no difference between the treatment groups (LSM difference = .000 [95% confidence interval (CI): −.69, .69], p = .9992). Furthermore, no differences between treatment groups were observed in the exploratory efficacy endpoints. Nivasorexant was well tolerated; the overall incidence of TEAEs was balanced between treatment groups, and the frequency of somnolence and fatigue in the nivasorexant group were similar to placebo.DiscussionIn this proof‐of‐concept study, 100 mg b.i.d. nivasorexant did not improve BE in adults with moderate to severe BED.Public SignificanceThe results of this Phase II study indicate that nivasorexant was well tolerated in adults with BED, but did not improve binge eating behavior over placebo. Further research is needed to improve our understanding of the role of the orexin‐1 receptor in BED.