bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing outcomes and cost in surgery versus watch & wait surveillance of patients with rectal cancer post neoadjuvant long course chemoradiotherapy
Authors: Crean Rory , Glyn Tamara , McCombie Andrew , Frizelle Frank 
Published: March 2024

AbstractBackgroundWatch and wait (W&W) in complete clinical responders after neoadjuvant chemoradiotherapy has increasingly robust data supporting its oncological safety. Recently, studies have assessed the real‐world costs of this strategy compared to surgical resection. Our aim was to compare our oncological safety and costs associated with operative and surveillance strategies to international literature.MethodsData were retrospectively collected and analysed via electronic health records from March 2014 to March 2021 in Christchurch, New Zealand. Two cohorts were created based on intention to treat. All hospital events were recorded and costed, as well as oncologic outcomes. Our primary endpoints were the cumulative cost of both strategies, 3‐year survival rate, and disease‐free survival.ResultsForty‐eight patients were identified who had rectal cancers resected (OT) with a yPT0N0 pathology, and 42 who were on the wait‐and‐watch (W&W) audit after having a clinical complete response. After exclusions, we identified 38 OT and 23 W&W patients; the W&W group were more co‐morbid (P = 0.05), had worse functional status (P = 0.008), higher BMI (P = 0.34) and more favourable clinical tumour staging (P = 0.01). The operative treatment (OT) group (n = 38) had more acute admissions (34% versus 13% in W&W, P = 0.08, OR 0.29). There was a 35.7% (n = 8 of 23) local recurrence in W&W and none in the OT group (P ≤ 0.001), with successful salvage in the W&W with local recurrence in 71.5% (n = 5 of 7). Three‐year distant metastasis‐free rate was 97.3% in the OT group and 90.9% in W&W (p = 0.05). Overall survival was 100% (W&W) and 94.7% (OT); (P = 0.019). Care in the OT group cost more than W&W, accounting for local regrowth management; $NZ70,759.56 versus $NZ47,905.52 (P = 0.014).ConclusionThis study found better oncological outcomes in the OT group, whilst the W&W group had reduced morbidity and acute bed days. The cost of wait and watch was approximately two‐thirds that of operative treatment, even accounting for salvage procedures for local regrowth.
Negative interactions and marital satisfaction across adulthood: The moderating role of affect valuation
Authors: Jiang Da , Li Tianyuan , Fung Helene H. 
Published: March 2024

AbstractOlder adults report higher marital satisfaction than younger adults even after negative interactions. The current study examined affect valuation as a potential moderator to explain age‐related differences in the relationship between negative interactions and marital satisfaction. We conducted a 14‐day daily diary study among 66 heterosexual couples (132 participants) aged from 21 to 80 years. At both person and daily levels, we found that valuing negative affect weakened the negative association between negative interactions and marital satisfaction in husbands. The moderating effect of negative affect valuation was stronger in older than younger husbands at the person but not daily level. Valuing positive affect more was associated with a stronger negative association between negative interactions and marital satisfaction in husbands at the person but not daily level. Such effect was again stronger in older than younger husbands. No significant results were found in wives. These findings shed light on the importance of affect valuation in understanding age‐related differences in marital dynamics.
Total laparoscopic wedge resection for an intramural ectopic pregnancy using an intraoperative ultrasound system: A case report
Authors: Kubo Kotaro , Fujikawa Atsushi , Mitoma Tomohiro , Mishima Sakurako , Ohira Akiko , Kirino Satoe , Maki Jota , Eto Eriko , Masuyama Hisashi 
Published: March 2024

AbstractIntramural pregnancy is a rare form of ectopic pregnancy, and the optimal treatment remains uncertain. We describe a 33‐year‐old woman (gravida 2, para 0) who visited our hospital with suspected ectopic pregnancy. The patient was asymptomatic and hemodynamically stable. Transvaginal ultrasonography revealed pregnancy at 6 weeks of gestation and a gestational sac and fetal heartbeat in the anterior muscular layer of the uterus, away from the endometrium. The fetal sac measured 26 mm. The serum human chorionic gonadotropin (hCG) level had increased to 27 655 mIU/mL. Accordingly, the patient was diagnosed with an intramural ectopic pregnancy and underwent total laparoscopic wedge resection using intraoperative ultrasonography. The postoperative course was uneventful, and she was discharged after 4 days. Her serum hCG level normalized at 26 days postoperatively. This case indicates that intraoperative laparoscopic ultrasonography seems viable for treating intramural pregnancies.
Navigating the Countertransference Experience: A Transtheoretical Specifist Model
Authors: Barreto João F. , Matos Paula Mena 
Published: March 2024

AbstractThe attempt to identify and classify distinct experiences falling under the common designation of countertransference has been labelled the specifist tradition. In this paper, a model describing two dimensions differentiating four components of countertransference experience is proposed. For each experiential component (subjective countertransference, objective countertransference, therapeutic attitude and emerging experience), a brief description based on previous literature from diverse theoretical fields is offered, along with clinical implications and illustrations and an account of empirical literature explicitly or implicitly addressing the specific component. In conclusion, the model is presented as a heuristic guide that can serve different purposes across different therapeutic orientations, with valuable implications for practice, training and supervision.
Cost‐effectiveness analysis of different treatment modalities in BCG‐unresponsive NMIBC
Authors: Rieger Constantin , Schlüchtermann Jörg , Storz Enno , Kastner Lucas , Pfister David , Heidenreich Axel 
Published: March 2024

ObjectiveRadical cystectomy (RC) is the standard of care (SOC) in BCG‐unresponsive NMIBC and is associated with a significant health‐related quality‐of‐life burden. Recently, promising results have been published on Gemcitabine/Docetaxel, Pembrolizumab, and Hyperthermic Intravesical Chemotherapy (HIVEC) as salvage therapy options trying to increase the rate of bladder preservation. Here, we performed a Cost‐Effectiveness‐Analysis of those treatment modalities.Patients and MethodsWe developed a Markov model from a payer's perspective drawing on clinical data of single‐arm trials testing intravesical gemcitabine/docetaxel and pembrolizumab in BCG‐unresponsive NMIBC, as well as clinical data from patients receiving hyperthermic intravesical chemotherapy HIVEC (n = 29) as intravesical salvage chemotherapy at our uro‐oncological centre in Cologne. Costs were simulated utilising a non‐commercial diagnosis‐related groups grouper, utilities were derived from comparable cost‐effectiveness studies. We used a Monte Carlo simulation to identify the optimal treatment, comparing the incremental cost effectiveness ratios (ICERs) at a willingness‐to‐pay threshold of €50 000 (euro)/quality‐adjusted life year (QALY).ResultsOver a horizon of 10 years, gemcitabine/docetaxel, HIVEC, and pembrolizumab were associated with costs of €48 353, €64 438, and €204 580, as well as a gain of QALYs of 6.16, 6.48, and 6.00, resulting in an ICER of €26 482, €42 567, and €184 533 respectively, in comparison to RC with total costs of €21 871 and a gain of QALYs of 5.01. Monte Carlo simulation identified HIVEC as the treatment of choice under assumption of a WTP of <€50 000.ConclusionConsidering a WTP of <€50 000/QALY, gemcitabine/docetaxel and HIVEC are highly cost‐effective therapeutic options in BCG‐refractory NMIBC, while RC remains the cheapest option. At its current price, pembrolizumab would only be cost‐effective assuming a price reduction of at least 70%.
Sulfonyl thiourea derivatives from 2‐aminodiarylpyrimidines: In vitro and in silico evaluation as potential carbonic anhydrase I, II, IX, and XII inhibitors
Authors: Thanh Nguyen Dinh , Giang Nguyen Thi Kim , Hai Do Son , Toan Vu Ngoc , Van Hoang Thi Kim , Tri Nguyen Minh 
Published: March 2024

AbstractA series of synthesized sulfonyl thiourea derivatives (7a–o) of substituted 2‐amino‐4,6‐diarylpyrimidines (4a–o) exhibited the remarkable inhibitory activity against some the human carbonic anhydrases (hCAs), including hCA I, II, IX, and XII isoforms. The inhibitory efficacy of synthesized sulfonyl thiourea derivatives were experimentally validated by in vitro enzymatic assays. 7a (KI = 46.14 nM), 7j (KI = 48.92 nM), and 7m (KI = 62.59 nM) (for isoform hCA I); 7f (KI = 42.72 nM), 7i (KI = 40.98 nM), and 7j (KI = 33.40 nM) (for isoform hCA II); 7j (KI = 228.5 nM), 7m (KI = 195.4 nM), and 7n (KI = 210.1 nM) (for isoform hCA IX); 7l (KI = 116.9 nM), 7m (KI = 118.8 nM), and 7n (KI = 147.2 nM) (for isoform hCA XII) in comparison with KI values of 452.1, 327.3, 437.2, and 338.9 nM, respectively, of the standard drug AAZ. These compounds also had significantly more potent inhibitory action against cytosolic isoform hCA I and tumor‐associated isoforms hCA IX and hCA XII. Furthermore, the potential inhibitory compounds were subjected to in silico screening for molecular docking and molecular dynamics simulations. The results of in vitro and in silico studies revealed that compounds 7a, 7j, and 7m were the most promising derivatives in this series due to their significant effects on studied hCA I, II, IX, and XII isoforms, respectively. The results showed that the sulfonyl thiourea moiety was accommodated deeply in the active site and interacted with the zinc ion in the receptors.
Understanding gut microbiome‐based machine learning platforms: A review on therapeutic approaches using deep learning
Authors: Malakar Shilpa , Sutaoney Priya , Madhyastha Harishkumar , Shah Kamal , Chauhan Nagendra Singh , Banerjee Paromita 
Published: March 2024

AbstractHuman beings possess trillions of microbial cells in a symbiotic relationship. This relationship benefits both partners for a long time. The gut microbiota helps in many bodily functions from harvesting energy from digested food to strengthening biochemical barriers of the gut and intestine. But the changes in microbiota composition and bacteria that can enter the gastrointestinal tract can cause infection. Several approaches like culture‐independent techniques such as high‐throughput and meta‐omics projects targeting 16S ribosomal RNA (rRNA) sequencing are popular methods to investigate the composition of the human gastrointestinal tract microbiota and taxonomically characterizing microbial communities. The microbiota conformation and diversity should be provided by whole‐genome shotgun metagenomic sequencing of site‐specific community DNA associating genome mapping, gene inventory, and metabolic remodelling and reformation, to ease the functional study of human microbiota. Preliminary examination of the therapeutic potency for dysbiosis‐associated diseases permits investigation of pharmacokinetic‐pharmacodynamic changes in microbial communities for escalation of treatment and dosage plan. Gut microbiome study is an integration of metagenomics which has influenced the field in the last two decades. And the incorporation of artificial intelligence and deep learning through “omics‐based” methods and microfluidic evaluation enhanced the capability of identification of thousands of microbes.
Supporting Latinx immigrant children and families in the transition to elementary school
Authors: Palacios Natalia , Paulick Judy 
Published: March 2024

AbstractCurrent approaches to supporting students in the transition to elementary school fail to meet the needs of Latinx immigrant children and their families in the United States. Typical approaches place the responsibility on families to help their children adapt to the expectations of their teacher, classroom, and school without recognizing the specific barriers to participation faced by Latinx immigrant parents. In this article, we describe these barriers and consider the ways community‐based practice can support and prioritize co‐constructed partnerships among teachers, schools, parents, and communities.
Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia
Authors: Cao Fuyang , Guo Yongxin , Guo Shuting , Hao Xinyu , Yang Lujia , Cao Jiangbei , Zhou Zhikang , Mi Weidong , Tong Li 
Published: March 2024

AbstractAimsGeneral anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTADA) to the PrL play a role in the transition from sevoflurane anesthesia to arousal. It is still uncertain whether the prelimbic cortex pyramidal neuron (PrLPyr) and its projections to VTA (PrLPyr‐VTA) are involved in anesthesia‐arousal regulation.MethodsWe employed chemogenetics and optogenetics to selectively manipulate neuronal activity in the PrLPyr‐VTA pathway. Electroencephalography spectra and burst‐suppression ratios (BSR) were used to assess the depth of anesthesia. Furthermore, the loss or recovery of the righting reflex was monitored to indicate the induction or emergence time of general anesthesia. To elucidate the receptor mechanisms in the PrLPyr‐VTA projection's impact on anesthesia and arousal, we microinjected NMDA receptor antagonists (MK‐801) or AMPA receptor antagonists (NBQX) into the VTA.ResultsOur findings show that chemogenetic or optogenetic activation of PrLPyr neurons prolonged anesthesia induction and promoted emergence. Additionally, chemogenetic activation of the PrLPyr‐VTA neural pathway delayed anesthesia induction and promoted anesthesia emergence. Likewise, optogenetic activation of the PrLPyr‐VTA projections extended the induction time and facilitated emergence from sevoflurane anesthesia. Moreover, antagonizing NMDA receptors in the VTA attenuates the delayed anesthesia induction and promotes emergence caused by activating the PrLPyr‐VTA projections.ConclusionThis study demonstrates that PrLPyr neurons and their projections to the VTA are involved in facilitating emergence from sevoflurane anesthesia, with the PrLPyr‐VTA pathway exerting its effects through the activation of NMDA receptors within the VTA.
Investigating the role of an immediate early gene FOS as a potential regulator of autophagic response to hypoglycemia in embryonic hypothalamic neurons
Authors: Ramakrishnan Rakhee K. , Srivastava Ankita , Rajan Reeja , Abusnana Salah , Mussa Bashair M. 
Published: March 2024

AbstractHypoglycemia‐associated autonomic failure (HAAF) is a well‐established complication of diabetes. Although HAAF has serious outcomes such as recurrent morbidity, coma, and death, the mechanisms of HAAF and its pathological components are largely unknown. Our previous studies have revealed that hypoglycemia is associated with the upregulation of an immediate early gene – FOS. In addition, it is documented that glucose deprivation activates neuronal autophagic activities. Therefore, the present study aimed to identify the role of FOS and one of the core components of the autophagy pathway, Beclin‐1 (encoded by the BECN1 gene), in the regulation of autophagic mechanisms in embryonic hypothalamic neurons in response to hypoglycemic conditions. Embryonic Mouse Hypothalamic Cell Line N39 (mHypoE‐N39 or N39) was cultured in reduced concentrations of glucose (2000, 900, 500, and 200 mg/L). Gene and protein expression, as well as immunofluorescence studies on autophagy were conducted under different reduced glucose concentrations in N39 hypothalamic neurons with and without FOS and BECN1 gene knockdowns (KD). The outcomes of the present study have demonstrated a significant increase in autophagosome formation and subsequent lysosomal degradation in the hypothalamic neurons in response to reduced glucose concentrations. This hypoglycemic response appears to be lowered to a similar extent in the FOS KD and BECN1 KD cells, albeit insignificantly from the negative control, is indicative of the involvement of FOS in the autophagic response of hypothalamic neurons to hypoglycemia. Moreover, the KD cells exhibited a change in morphology and reduced cell viability compared with the control cells. Our findings suggest that reduced FOS expression could potentially be associated with impaired autophagic activities that are dependent on BECN1, which could lead to decreased or blunted hypothalamic activation in response to hypoglycemia, and this, in turn, may contribute to the development of HAAF.
Bioavailability of three novel oral, sustained‐release pellets, relative to an immediate‐release tablet containing 500 mg flucytosine: A randomized, open‐label, crossover study in healthy volunteers
Authors: Goyal Vishal , Krantz Edrich , Simon Francois , Neven Anouk , Eriksson Johanna , Saayman Amaria , Ibnou Zekri Lassout Nabila , Louis Mathieu , Robinson Stephen , Deshmukh Abhijit , Antarkar Amit , Ruffell Carol , Victor Sarika , Chenel Marylore , Celebic Aljosa , Caplain Henri , Gillon Jean‐Yves , Ribeiro Isabela 
Published: March 2024

AbstractThe opportunistic fungal infection cryptococcal meningoencephalitis is a major cause of death among people living with HIV in sub‐Saharan Africa. We report pharmacokinetic (PK) and safety data from a randomized, four‐period crossover phase I trial of three sustained‐release (SR) oral pellet formulations of 5‐flucytosine conducted in South Africa. These formulations were developed to require less frequent administration, to provide a convenient alternative to the current immediate release (IR) formulation, A. Formulations B, C, and D were designed to release 5‐flucytosine as a percentage of the nominal dose in vitro. We assessed their safety and PK profiles in a single dose (1 × 3000 mg at 0 h), relative to commercial IR tablets (Ancotil 500 mg tablets; 3 × 500 mg at 0 h and 3 × 500 mg at 6 h) in healthy, fasted participants. Forty‐two healthy participants were included. All treatments were well‐tolerated. The primary PK parameters, maximum observed plasma concentration (Cmax) and area under the concentration‐time profiles, were significantly lower for the SR formulations than for the IR tablets, and the geometric mean ratios fell outside the conventional bioequivalence limits. The median maximum time to Cmax was delayed for the SR pellets. Physiologically‐based PK modeling indicated a twice‐daily 6400 mg dose of SR formulation D in fasted condition would be optimal for further clinical development. This regimen is predicted to result in a rapid steady‐state plasma exposure with effective and safe trough plasma concentration and Cmax values, within the therapeutic boundaries relative to plasma exposure after four times per day administration of IR tablets (PACTR202201760181404).
FAK mediates hypoxia‐induced pulmonary artery smooth muscle cell proliferation by modulating mitochondrial transcription termination factor 1/cyclin D1
Authors: Lin Chunlong , Yang Hui , Luo Qiong , Liu Qi 
Published: March 2024

AbstractThis study aimed to investigate the mechanism of FAK‐dependent hypoxia‐induced proliferation on human pulmonary artery smooth muscle cells (HPASMCs). Primary HPASMCs were isolated and cultured in vitro under normal and hypoxia conditions to assess cell proliferation with cell counting kit‐8. FAK and mitochondrial transcription termination factor 1 (mTERF1) were silenced with siRNA, mRNA, and protein levels of FAK, mTERF1, and cyclin D1 were determined. HPASMC proliferation increased under hypoxia compared to normal conditions. Knocking down FAK or mTERF1 with siRNA led to decreased cell proliferation under both normal and hypoxia conditions. FAK knockdown led to the reduction of both mTERF1 and cyclin D1 expressions under the hypoxia conditions, whereas mTERF1 knockdown led to the downregulation of cyclin D1 expression but not FAK expression under the same condition. However, under normal conditions, knocking down either FAK or mTERF1 had no impact on cyclin D1 expression. These results suggested that FAK may regulate the mTERF1/cyclin D1 signaling pathway to modulate cell proliferation in hypoxia.
Heterogeneity and Labour Agency in Artisanal and Small‐scale Gold Mining in the Democratic Republic of Congo
Authors: Geenen Sara , Bikubanya Divin‐Luc 
Published: March 2024

ABSTRACTThis article considers the broad question of how to improve the conditions of workers in artisanal and small‐scale gold mining (ASGM), which relies on predominantly informal activities. While acknowledging that formalization can provide ASGM miners with tenure security and protection of labour rights, it is important to highlight that not all workers are likely to benefit from formalization in the same way, and that decent work ambitions should extend to all workers, regardless of whether or not they are formalized. It is therefore crucial to understand the heterogeneity in the ASGM workforce. This article describes working conditions for different categories of workers based on a survey carried out in the Watsa and Shabunda territories in Eastern Democratic Republic of Congo. It analyses labour agency and shows that workers are diversely integrated in the labour process and may use power resources in various ways. The discussion reflects on ways to consider the heterogeneity in ASGM labour and to push the ASGM agenda beyond formalization.
Efficacy of 1‐hour postload plasma glucose as a suitable measurement in predicting type 2 diabetes and diabetes‐related complications: A post hoc analysis of the 30‐year follow‐up of the Da Qing IGT and Diabetes Study
Authors: Peng Minying , He Siyao , Wang Jinping , An Yali , Qian Xin , Zhang Bo , Zhang Lihong , Chen Bo , Yang Zhiwei , Li Guangwei , Gong Qiuhong ,   for the Da Qing Diabetes Prevention Outcome Study Group
Published: March 2024

AbstractAimTo evaluate whether 1‐hour plasma glucose (1hPG) can be a comparable measurement to 2‐hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes.MethodsA total of 1026 non‐diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6‐, 20‐ and 30year follow‐up for outcomes including diabetes, all‐cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a ‘1hPG‐normal’ group (1hPG <8.6 mmol/L) and a ‘1hPG‐high’ group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time‐dependent receiver‐operating characteristic (ROC) curve.ResultsCompared with the 1hPG‐normal group, the 1hPG‐high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43–5.79), all‐cause mortality (HR 1.46, 95% CI 1.07–2.01), CVD mortality (HR 1.84, 95% CI 1.16–2.95), CVD events (HR 1.39, 95% CI 1.03–1.86) and microvascular disease (HR 1.70, 95% CI: 1.03–2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long‐term follow‐up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009).ConclusionsElevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long‐term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.