bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate‐specific membrane antigen positron emission tomography detected local failure after post‐prostatectomy radiation therapy: Low rates of out‐of‐field recurrence validates current Australian prostate bed contouring guidelines
Authors: Shakespeare Thomas Philip , Yap Shaun Zheng Liang , Hsieh Michael , Tahir Abdul Rahim Mohd , Armstrong Shreya 
Published: July 2023

AbstractIntroductionThe Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post‐prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate‐specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate‐specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines.MethodsAt our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re‐staged using PSMA PET imaging. We identified patients with PET‐avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines.ResultsNinety‐four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local‐only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy‐three (77.7%) patients had a component of node failure, with 56 (59.6%) having node‐only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time.ConclusionThe low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.
A phase II study of a doublet metronomic chemotherapy regimen consisting of oral vinorelbine and capecitabine in Chinese women with HER2‐negative metastatic breast cancer
Authors: Chai Yue , Liu Jiaxuan , Jiang Mingxia , He Maiyue , Wang Zijing , Ma Fei , Wang Jiayu , Yuan Peng , Luo Yang , Xu Binghe , Li Qiao 
Published: July 2023

AbstractBackgroundThis single‐arm prospective phase II trial was performed to assess the efficacy and safety of the dual oral metronomic vinorelbine and capecitabine (mNC) regimen in women with HER2‐negative metastatic breast cancer (MBC) in China.MethodsThe mNC regimen was administered to the enrolled cases, including oral vinorelbine (VNR) 40 mg three times weekly (on days 1, 3 and 5 every week) and capecitabine (CAP) 500 mg three times a day, until disease progression or intolerable toxicity. The primary endpoint was the 1‐year progression‐free survival (PFS) rate. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and treatment‐related adverse events (TRAEs). Stratified factors included treatment lines and hormone receptor (HR) status.ResultsBetween June 2018 and March 2023, 29 patients were enrolled into the study. The median follow‐up time was 25.4 months (range, 2.0–53.8). In the entire group, the 1‐year PFS rate was 54.1%. ORR, DCR and CBR were 31.0%, 96.6% and 62.1%, respectively. The mPFS was 12.5 months (range, 1.1–28.1). Subgroup analysis revealed that ORRs were 29.4% and 33.3% in first‐ and ≥second‐line chemotherapy, respectively. ORRs were 29.2% (7/24) and 40.0% (2/5) for HR‐positive MBC and metastatic triple‐negative breast cancer (mTNBC), respectively. Grade 3/4 TRAEs were neutropenia (10.3%) and nausea/vomiting (6.9%).ConclusionsThe dual oral mNC regimen showed very good safety features and improved compliance without loss of efficacy in both first‐ and second‐line treatments. The regimen also reached an excellent ORR in the mTNBC subgroup.
Alcohol sensitivity and tolerance encoding in sleep regulatory circadian neurons in Drosophila
Authors: Lange Anthony P. , Wolf Fred W. 
Published: July 2023

AbstractAlcohol tolerance is a simple form of behavioural and neural plasticity that occurs with the first drink. Neural plasticity in tolerance is likely a substrate for longer term adaptations that can lead to alcohol use disorder. Drosophila develop tolerance with characteristics similar to vertebrates, and it is a useful model for determining the molecular and circuit encoding mechanisms in detail. Rapid tolerance, measured after the first alcohol exposure is completely metabolized, is localized to specific brain regions that are not interconnected in an obvious way. We used a forward neuroanatomical screen to identify three new neural sites for rapid tolerance encoding. One of these was composed of two groups of neurons, the DN1a and DN1p glutamatergic neurons, that are part of the Drosophila circadian clock. We localized rapid tolerance to the two DN1a neurons that regulate arousal by light at night, temperature‐dependent sleep timing, and night‐time sleep. Two clock neurons that regulate evening activity, LNd6 and the 5th LNv, are postsynaptic to the DN1as, and they promote rapid tolerance via the metabotropic glutamate receptor. Thus, rapid tolerance to alcohol overlaps with sleep regulatory neural circuitry, suggesting a mechanistic link.
EGCG attenuates METH self‐administration and reinstatement of METH seeking in mice
Authors: Si Zizhen , Wang Xidi , Yu Zhaoying , Ruan Yuer , Qian Liyin , Lin Shujun , Gong Xinshuang , Li Longhui , Huang Jing , Liu Yu 
Published: July 2023

AbstractMethamphetamine (METH) use disorder is a chronic, relapsing disorder and involves frequent failures of self‐control of drug seeking and taking. Epigallocatechin‐3‐gallate (EGCG) is the most abundant polyphenolic compounds of green tea, which has shown great therapeutic effectiveness in neurological disorders. However, it is still unknown whether and how EGCG affects METH seeking behaviour. Here, we show nanostructured EGCG/ascorbic acid nanoparticles (EGCG/AA NPs) dose‐dependently reduced METH self‐administration (SA) under fixed‐ratio 1 (FR1) and progressive ratio (PR) reinforcement schedules in mice and shifted METH dose–response curves downward. Furthermore, EGCG/AA NPs decreased drug‐ and cue‐induced METH seeking. In addition, we found that METH SA led to a decrease in inhibitory postsynaptic currents (IPSCs) and increase in the AMPAR/NMDAR ratio and excitation/inhibition (E/I) ratio in ex vivo midbrain slices from ventral tegmental area (VTA) dopamine neurons. EGCG/AA NPs enhanced Gamma‐aminobutyric acid (GABA)ergic inhibition and normalized the E/I ratio. EGCG restored the balance between excitation and inhibition in VTA dopamine neurons, which may contribute to the attenuation of METH SA. These findings indicate that EGCG is a promising pharmacotherapy for METH use disorder.
Comprehensive evaluation of hematospermia in patients with acute epididymitis compared to patients with isolated hematospermia
Authors: Dittmar Florian , Rosellen Jens , Reiser Leo , Fritzenwanker Moritz , Hauptmann Arne , Diemer Thorsten , Schuppe Hans‐Christian , Wagenlehner Florian , Pilatz Adrian 
Published: July 2023

AbstractBackgroundAmong the most commonly known causes of hematospermia are infections in the genitourinary tract, but no study exists that has comprehensively investigated hematospermia in patients with acute epididymitis.ObjectivesTo assess the impact of hematospermia in patients with acute epididymitis and its association with clinical, microbiological, and semen parameters.Materials and methodsSince May 2007, a total of 324 sexually active patients with acute epididymitis were recruited in a prospective cohort study. Patients received a comprehensive medical and sexual history, and clinical, sonographic, laboratory, and microbiological diagnostics. Antibiotic therapy was given according to European Association of Urology guidelines. Semen analysis was offered 14 days after the first presentation and initiation of therapy. Since 2013, a separate control group of 56 patients presenting with isolated hematospermia (= no other urogenital symptoms) was prospectively recruited, and differences between the groups were statistically evaluated.ResultsOf 324 patients with acute epididymitis, 50 patients (15%) had self‐reported hematospermia. This occurred with a median of 24 h before the onset of scrotal symptoms and was associated with significantly elevated prostate‐specific antigen levels compared to 274 patients without hematospermia (3.1 vs. 1.8 ng/ml, p < 0.01). The two most common etiological pathogens were Escherichia coli and Chlamydia trachomatis, and the bacterial spectrum was comparable in both epididymitis subgroups (p = 0.859). Semen analysis at 14 days still showed hematospermia in 24% of patients associated with massive leukocytospermia. Compared to the hematospermia control group, the two epididymitis subgroups showed significantly increased inflammation markers (pH, leukocytes, and elastase), reduced sperm concentration, and reduced levels of alpha‐glucosidase and zinc (always p < 0.01).Discussion and conclusionIn sexually active patients who develop acute epididymitis, self‐reported hematospermia is evident in 15% of patients as early as one day before the onset of scrotal symptoms. Conversely, none of the 56 patients presenting with isolated hematospermia developed epididymitis within the next 4 weeks.
Outcomes after interruption of targeted therapy in patients with histiocytic neoplasms
Authors: Reiner Anne S. , Durham Benjamin H. , Yabe Mariko , Petrova‐Drus Kseniya , Francis Jasmine H. , Rampal Raajit K. , Lacouture Mario E. , Rotemberg Veronica , Abdel‐Wahab Omar , Panageas Katherine S. , Diamond Eli L. 
Published: July 2023

SummaryLittle is known about outcomes following interruption of targeted therapy in adult patients with histiocytic neoplasms. This is an IRB‐approved study of patients with histiocytic neoplasms whose BRAF and MEK inhibitors were interrupted after achieving complete or partial response by 18‐fluorodeoxyglucose positron emission tomography (FDG‐PET). 17/22 (77%) of patients experienced disease relapse following treatment interruption. Achieving a complete response prior to interruption, having a mutation other than BRAFV600E, and receiving MEK inhibition only were each associated with a statistically significant improvement in relapse‐free survival. Relapse is common following treatment interruption however some patients may be suitable for limited‐duration treatment.
N6‐methyladenosine‐modified FAM111A‐DT promotes hepatocellular carcinoma growth via epigenetically activating FAM111A
Authors: Pu Jian , Xu Zuoming , Huang Youguan , Nian Jiahui , Yang Meng , Fang Quan , Wei Qing , Huang Zihua , Liu Guoman , Wang Jianchu , Wu Xianjian , Wei Huamei 
Published: July 2023

AbstractAs an epitranscriptomic modulation manner, N6‐methyladenosine (m6A) modification plays important roles in various diseases, including hepatocellular carcinoma (HCC). m6A modification affects the fate of RNAs. The potential contributions of m6A to the functions of RNA still need further investigation. In this study, we identified long noncoding RNA FAM111A‐DT as an m6A‐modified RNA and confirmed three m6A sites on FAM111A‐DT. The m6A modification level of FAM111A‐DT was increased in HCC tissues and cell lines, and increased m6A level was correlated with poor survival of HCC patients. m6A modification increased the stability of FAM111A‐DT transcript, whose expression level showed similar clinical relevance to that of the m6A level of FAM111A‐DT. Functional assays found that only m6A‐modified FAM111A‐DT promoted HCC cellular proliferation, DNA replication, and HCC tumor growth. Mutation of m6A sites on FAM111A‐DT abolished the roles of FAM111A‐DT. Mechanistic investigations found that m6A‐modified FAM111A‐DT bound to FAM111A promoter and also interacted with m6A reader YTHDC1, which further bound and recruited histone demethylase KDM3B to FAM111A promoter, leading to the reduction of the repressive histone mark H3K9me2 and transcriptional activation of FAM111A. The expression of FAM111A was positively correlated with the m6A level of FAM111A‐DT, and the expression of methyltransferase complex, YTHDC1, and KDM3B in HCC tissues. Depletion of FAM111A largely attenuated the roles of m6A‐modified FAM111A‐DT in HCC. In summary, the m6A‐modified FAM111A‐DT/YTHDC1/KDM3B/FAM111A regulatory axis promoted HCC growth and represented a candidate therapeutic target for HCC.
Trabecular bone score and bone mineral density as indices of skeletal fragility in endogenous Cushing's syndrome
Authors: Boro Hiya , Mannar Velmurugan , Malhotra Rakhi , Alam Sarah , Khatiwada Saurav , Kubihal Suraj , Dogra Vinay , Golla Kiran Kumar , Mathew Uthara Elsa , Halebidu Tejaswi , Attri Bhawna 
Published: July 2023

AbstractObjectiveEndogenous Cushing's syndrome (CS) is a known cause of secondary osteoporosis. Vertebral fractures (VFs) in endogenous CS may occur despite normal bone mineral density (BMD). Trabecular bone score (TBS) is a relatively new, non‐invasive technique to assess bone microarchitecture. The objective of our study was to analyse the BMD and bone microarchitecture using TBS in endogenous CS and compare it with a group of age and sex‐matched healthy controls, and also analyse the factors predicting BMD and TBS.DesignCross‐sectional study of cases and controls.Patients and measurementsWe included 40 female patients with overt endogenous CS, out of which 32 were adrenocorticotropic hormone (ACTH)‐dependent CS and 8 were ACTH‐independent. We also included 40 healthy, female controls. Both patients and controls were subjected to an assessment of biochemical parameters and BMD and TBS.ResultsPatients with endogenous CS had significantly lower BMD at the lumbar spine, femoral neck, and total hip and significantly lower TBS than healthy controls (all p < .001), while no significant difference was noted in the distal radius BMD (p = .055). In endogenous CS, a large proportion of patients, n = 13 (32.5%) had normal BMD for age (BMD Z‐score ≥ −2.0) with low TBS (L1‐L4 TBS ≤ 1.34). TBS correlated negatively with HbA1c (p = .006), and positively with serum T4 (p = .027).ConclusionTBS should be considered an important complementary tool in addition to BMD for the routine assessment of skeletal health in CS.
Electroacupuncture alleviates mechanical allodynia and anxiety‐like behaviors induced by chronic neuropathic pain via regulating rostral anterior cingulate cortex‐dorsal raphe nucleus neural circuit
Authors: Xu Yingling , Zhu Xixiao , Chen Yuerong , Chen Yeqing , Zhu Yichen , Xiao Siqi , Wu Mengwei , Wang Yifang , Zhang Chi , Wu Zenmin , He Xiaofen , Liu Boyu , Shen Zui , Shao Xiaomei , Fang Jianqiao 
Published: July 2023

AbstractAimsEpidemiological studies in patients with neuropathic pain have demonstrated a strong association between neuropathic pain and psychiatric conditions such as anxiety. Preclinical and clinical work has demonstrated that electroacupuncture (EA) effectively alleviates anxiety‐like behaviors induced by chronic neuropathic pain. In this study, a potential neural circuitry underlying the therapeutic action of EA was investigated.MethodsThe effects of EA stimulation on mechanical allodynia and anxiety‐like behaviors in animal models of spared nerve injury (SNI) were examined. EA plus chemogenetic manipulation of glutamatergic (Glu) neurons projecting from the rostral anterior cingulate cortex (rACCGlu) to the dorsal raphe nucleus (DRN) was used to explore the changes of mechanical allodynia and anxiety‐like behaviors in SNI mice.ResultsElectroacupuncture significantly alleviated both mechanical allodynia and anxiety‐like behaviors with increased activities of glutamatergic neurons in the rACC and serotoninergic neurons in the DRN. Chemogenetic activation of the rACCGlu‐DRN projections attenuated both mechanical allodynia and anxiety‐like behaviors in mice at day 14 after SNI. Chemogenetic inhibition of the rACCGlu‐DRN pathway did not induce mechanical allodynia and anxiety‐like behaviors under physiological conditions, but inhibiting this pathway produced anxiety‐like behaviors in mice at day 7 after SNI; this effect was reversed by EA. EA plus activation of the rACCGlu‐DRN circuit did not produce a synergistic effect on mechanical allodynia and anxiety‐like behaviors. The analgesic and anxiolytic effects of EA could be blocked by inhibiting the rACCGlu‐DRN pathway.ConclusionsThe role of rACCGlu‐DRN circuit may be different during the progression of chronic neuropathic pain and these changes may be related to the serotoninergic neurons in the DRN. These findings describe a novel rACCGlu‐DRN pathway through which EA exerts analgesic and anxiolytic effects in SNI mice exhibiting anxiety‐like behaviors.
Novel approach toward minimally invasive surgery for mid‐transverse colon cancer: ‘moving the left colon’ technique
Authors: Iguchi Kenta , Sugano Nobuhiro , Sugiyama Atsuhiko , Saito Kentaro , Atsumi Yosuke , Kazama Keisuke , Numata Masakatsu , Mushiake Hiroyuki , Sato Tsutomu , Rino Yasushi 
Published: July 2023

AbstractAimDuring surgery for mid‐transverse colon cancer (MTC), surgeons often face the dilemma of whether to mobilize the hepatic or splenic flexure. There is no established optimal minimally invasive surgical procedure for MTC.MethodsWe present our novel minimally invasive surgical technique, called the ‘moving the left colon’ technique for MTC, along with a video demonstration. The procedure involves four main steps: (i) mobilization of the splenic flexure using a medial‐to‐lateral approach, (ii) dissection of lymph nodes around the middle colic artery from the left side of the superior mesenteric artery approach, (iii) separation of the pancreas and transverse mesocolon and (iv) ‘moving the left colon’ and performing an intracorporeal anastomosis. By mobilizing the splenic flexure, anatomical landmarks are revealed, which enables safer dissection. Combining this technique with intracorporeal anastomosis allows for a safe and easy anastomosis.ResultsBetween April 2021 and January 2023, a single‐skilled colorectal surgeon performed laparoscopic transverse colectomies using our new approach on three consecutive patients with MTC. The patients had a median age of 75 years (range 46–89 years). The median operative time was 194 min (range 193–228 min) and blood loss was 8 mL (range 0–20 mL). None of the patients experienced any perioperative complications and the median postoperative hospital stay was 6 days.ConclusionWe introduced a novel approach for laparoscopic surgery for MTC. This technique can be performed safely and may help standardize minimally invasive surgery for MTC.
Limited Evidence of an Association Between Language, Literacy, and Procedural Learning in Typical and Atypical Development: A Meta‐Analysis
Authors: Oliveira Cátia M. , Henderson Lisa M. , Hayiou‐Thomas Marianna E. 
Published: July 2023

AbstractThe ability to extract patterns from sensory input across time and space is thought to underlie the development and acquisition of language and literacy skills, particularly the subdomains marked by the learning of probabilistic knowledge. Thus, impairments in procedural learning are hypothesized to underlie neurodevelopmental disorders, such as dyslexia and developmental language disorder. In the present meta‐analysis, comprising 2396 participants from 39 independent studies, the continuous relationship between language, literacy, and procedural learning on the Serial Reaction Time task (SRTT) was assessed across children and adults with typical development (TD), dyslexia, and Developmental Language Disorder (DLD). Despite a significant, but very small, relationship between procedural learning and overall language and literacy measures, this pattern was not observed at the group‐level when examining TD, dyslexic, and DLD groups separately. Based on the procedural/declarative model, a positive relationship was expected between procedural learning and language and literacy measures for the typically developing group; however, no such relationship was observed. This was also the case for the disordered groups (ps > .05). Also counter to expectations, the magnitude of the relationship between procedural learning and grammar and phonology did not differ between TD and DLD (ps > .05), nor between the TD and dyslexic group on reading, spelling, and phonology (ps > .05). While lending little support to the procedural/declarative model, we consider that these results may be the consequence of poor psychometric properties of the SRTT as a measure of procedural learning.
Who supports drug‐checking services in Australia? An analysis of 2019 National Drug Strategy Household Survey data
Authors: Caluzzi Gabriel , Torney Alexandra , Callinan Sarah 
Published: July 2023

AbstractIntroductionDrug‐checking services can minimise the potential harms from drug use and have received increased attention in recent policy debates in Australia. In this brief report, we aim to better understand the prevalence of support for drug‐checking services among individuals of certain demographic groups, social status and social attitudes towards drug and alcohol policy.MethodsThis report uses data from the 2019 National Drug Strategy Household Survey, a national population study of alcohol and other drug use conducted triennially in Australia. We examined support for drug‐checking services descriptively, alongside associations between demographic, social and substance use variables and support of drug‐checking using Generalised Linear Model analyses with a Poisson distribution and log link.ResultsOverall, 56% of the sample supported policies related to drug‐checking services. Support was highest among those aged 25–34 years (62%), most socioeconomically advantaged (66%), with an income over $104,000 (64%), with a bachelor's degree or higher (65%), living in major cities (58%), recent consumers of commonly tested drugs (88%) and other drugs (77%), and risky drinkers (64%). In the multivariable model, those who were younger, women and had the highest level of education were more likely to support the policy compared to those who were aged 55+ years, men and had lower levels of education.Discussion and ConclusionThis report highlights that, while there were different degrees of support based on demographic characteristics, substance use status and social attitudes towards drug and alcohol policy, the overall majority of the sample supported the provision of drug‐checking services.