bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using piospheres to identify, assess and monitor gradients of elephant impact on thicket
Authors: Carvalho Shandon Luke , Campbell Eileen Elaine 
Published: March 2023

AbstractOverpopulation in conservation areas with large populations of elephants reduces the diversity of the thicket vegetation of the Eastern Cape Province of South Africa. Monitoring species' specific impacts is a difficult task for reserves. This study investigates whether the Normalised Difference Vegetation Index (NDVI) can be used to evaluate the health of thicket in the Addo Elephant National Park successfully. To achieve this, different browsing intensities of elephants were used to establish a gradient of the full range of utilisation levels on thicket. These were obtained at different distances from the nearest available water sources for Mesic and Valley Thicket types. NDVI values were correlated to an elephant utilisation gradient, which was, in turn, directly related to distance from a water source. The lowest NDVI values (<0.2) were observed adjacent to watering holes where vegetation was completely degraded due to trampling by the daily congregation of animals. The highest NDVI values (>0.5 representing the densest stands of thicket vegetation) were obtained at distances exceeding 7 km from a water source where elephant densities were the lowest within the park. NDVI values could, therefore, be used to identify and monitor gradients of elephant impact on the integrity of thicket.
Entecavir versus tenofovir on prognosis of hepatitis B virus‐related hepatocellular carcinoma after curative hepatectomy
Authors: Kao Wei‐Yu , Tan Elise Chia‐Hui , Lee Hsin‐Lun , Huang Yi‐Hsiang , Huo Teh‐Ia , Chang Chun‐Chao , Chiou Jeng‐Fong , Hou Ming‐Chih , Wu Jaw‐Ching , Su Chien‐Wei 
Published: March 2023

SummaryBackgroundThere is still controversy about whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have different effects on the outcomes of patients with hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC).AimsThe aim of this study was to compare the prognoses between ETV and TDF treatment among patients with HBV‐related HCC after hepatectomy.MethodsAn analysis was done on data from the Taiwan Cancer Registry, which was linked to Taiwan National Health Insurance Research Database, for the years 2011–2016. We identified 7107 patients with HBV‐related HCC after curative hepatectomy, and 25.3% of them used ETV or TDF after surgery. After propensity score overlap weighting, 1797 patients treated with ETV (n = 1365) or TDF (n = 432) were included for analyses. Cox proportional hazards models were used to compare the efficacy of ETV and TDF for recurrence and overall survival (OS).ResultsAfter hepatectomy, the recurrence rate per 100 person‐years was 14.87 for the ETV group and 9.25 for the TDF group. The risk of recurrence was similar in the TDF group and the ETV group (HR [95% CI]: 0.91 [0.69–1.19; p = 0.479]), as was the risk of all‐cause mortality (HR [95% CI]: 0.67 [0.42–1.07]; p = 0.091). When considering early recurrence (<2 years) and late recurrence (≧2 years), the TDF and ETV groups showed no significant differences. Subgroup analyses and sensitivity analyses demonstrated consistent results.ConclusionBoth TDF and ETV showed similar health benefits in terms of recurrence and OS in patients with HBV‐related HCC patients after hepatectomy.
Prevalence and impact of faecal incontinence among individuals with Rome IV irritable bowel syndrome
Authors: Goodoory Vivek C. , Ng Cho E. , Black Christopher J. , Ford Alexander C. 
Published: March 2023

SummaryBackgroundLittle is known about faecal incontinence (FI) in individuals with irritable bowel syndrome (IBS).AimsTo compare characteristics of people with IBS reporting FI, compared with people with IBS who do not report FI.MethodsWe collected demographic, gastrointestinal and psychological symptoms, healthcare usage, direct healthcare costs, impact on work and activities of daily living, and quality of life data from individuals with Rome IV‐defined IBS. We asked participants about FI, assigning presence or absence according to Rome‐IV criteria.ResultsOf 752 participants with Rome IV IBS, 202 (26.9%) met Rome IV criteria for FI. Individuals with FI were older (p < 0.001), more likely to have IBS‐D (47.0% vs. 39.0%, p = 0.008), and less likely to have attained a university or postgraduate level of education (31.2% vs. 45.6%, p < 0.001), or to have an annual income of ≥£30,000 (18.2% vs. 32.9%, p < 0.001). They were more likely to report urgency (44.6% vs. 19.1%, p < 0.001) as their most troublesome symptom and a greater proportion had severe IBS symptom scores, abnormal depression scores, higher somatic symptom‐reporting scores or higher gastrointestinal symptom‐specific anxiety scores (p < 0.01 for trend for all analyses). Mean health‐related quality of life scores were significantly lower among those with, compared with those without, FI (p < 0.001). Finally, FI was associated with higher IBS‐related direct healthcare costs (p = 0.002).ConclusionsAmong individuals with Rome IV IBS, one‐in‐four repo rted FI according to Rome IV criteria. Physicians should ask patients with IBS about FI routinely.
Social work for vulnerable and marginalized people during COVID‐19 in Japan
Authors: Murayama Yoh , Hasebe Masami , Yamazaki Sachiko , Yamaguchi Jun , Kobayashi Erika 
Published: March 2023

AbstractDuring the Coronavirus disease pandemic (COVID‐19), working conditions became increasingly difficult for social workers, as they had to deal with new challenges and added workloads. This study describes the difficulties faced by social workers of the Self‐Reliance Support System in Japan and clarifies the solution for each difficulty while conducting their duties to support vulnerable people during COVID‐19. To this end, we conducted an open‐ended questionnaire survey and an interview survey. The data were analyzed using qualitative coding. The results showed that the difficulties faced in consultation support work included supporting hitherto socially invisible groups such as sole traders and foreigners. Social workers also faced an ethical dilemma, as they could not provide support to clients who “did not try to solve their problems” or for whom “interventional attempts did not lead to counseling support” and who only sought benefits at the risk of becoming isolated and impoverished. Following this, consultants collaborated to resolve such difficulties while maximizing the use of various local resources. The study's findings clarify that it would be effective to understand the difficulties faced by social workers to obtain hints toward their resolution.
CYP11B2 inhibitor dexfadrostat phosphate suppresses the aldosterone‐to‐renin ratio, an indicator of sodium retention, in healthy volunteers
Authors: Mulatero Paolo , Groessl Michael , Vogt Bruno , Schumacher Christoph , Steele Ronald Edward , Brooks Ashley , Hossack Stuart , Brunner Hans‐Rudolf 
Published: March 2023

AimsHigh aldosterone is a key driver of hypertension and long‐term negative sequelae. We evaluated the safety and efficacy of dexfadrostat phosphate (DP13), a novel aldosterone synthase (CYP11B2) inhibitor, in healthy participants.MethodsThis randomized, double‐blind, placebo‐controlled study was conducted in two parts. In part A, a single‐ascending dose escalation, 16 participants received oral DP13 1–16 mg. Part B was a multiple‐ascending dose, sequential group study in which 32 participants received oral DP13 4, 8 or 16 mg once daily for 8 days. Safety and tolerability were monitored throughout. An adrenocorticotropic hormone (ACTH) stimulation test at maximal blood drug concentrations defined the dose range for multiple dosing.ResultsDP13 was well tolerated at all doses, with no serious adverse events. In part B, all DP13 doses (4, 8 and 16 mg) over 8 days effectively suppressed aldosterone production, increased the urinary sodium/potassium ratio, decreased plasma sodium and increased plasma potassium and renin levels compared with placebo, resulting in potent suppression of the aldosterone‐to‐renin ratio (ARR). Endocrine counter‐regulation resulted in the 4 mg dose no longer sustaining 24‐h aldosterone suppression after 8 days of treatment, unlike the 8‐ and 16 mg doses. There was no evidence of drug‐induced adrenal insufficiency (ACTH stress challenge).ConclusionsIn patients with excess aldosterone and ensuing sodium retention driving hypertension, managing sodium balance is critical. A CYP11B2 inhibitor like DP13, whose effectiveness can be monitored by a reduction in ARR, may prove valuable in managing aldosterone‐dependent hypertension and primary aldosteronism.
Abemaciclib drives the therapeutic differentiation of acute myeloid leukaemia stem cells
Authors: Xie Xiaoling , Zhang Wuju , Zhou Xuan , Ye Zhixin , Wang Hao , Qiu Yingqi , Pan Yating , Hu Yuxing , Li Luyao , Chen Zhuanzhuan , Yang Wanwen , Lu Yao , Zou Shuxin , Li Yuhua , Bai Xiaochun 
Published: March 2023

SummarySelf‐renewal and differentiation arrest are two features of leukaemia stem cells (LSCs) responsible for the high relapse rate of acute myeloid leukaemia (AML). To screen drugs to overcome differentiation blockade for AML, we conducted screening of 2040 small molecules from a library of United States Food and Drug Administration‐approved drugs and found that the cyclin‐dependent kinase (CDK)4/6 inhibitor, abemaciclib, exerts high anti‐leukaemic activity. Abemaciclib significantly suppressed proliferation and promoted the differentiation of LSCs in vitro. Abemaciclib also efficiently induced differentiation and impaired self‐renewal of LSCs, thus reducing the leukaemic cell burden and improving survival in various preclinical animal models, including patient‐derived xenografts. Importantly, abemaciclib strongly enhanced anti‐tumour effects in combination with venetoclax, a B‐cell lymphoma 2 (Bcl‐2) inhibitor. This treatment combination led to a marked decrease in LSC‐enriched populations and resulted in a synergistic anti‐leukaemic effect. Target screening revealed that in addition to CDK4/6, abemaciclib bound to and inhibited CDK9, consequently attenuating the protein levels of global p‐Ser2 RNA Polymerase II (Pol II) carboxy terminal domain (CTD), Myc, Bcl‐2, and myeloid cell leukaemia‐1 (Mcl‐1), which was important for the anti‐AML effect of abemaciclib. Collectively, these data provide a strong rationale for the clinical evaluation of abemaciclib to induce LSC differentiation and treat highly aggressive AML as well as other advanced haematological malignancies.
Ejaculatory function following transperineal laser ablation vs TURP for benign prostatic obstruction: a randomized trial
Authors: Bertolo Riccardo , Iacovelli Valerio , Cipriani Chiara , Carilli Marco , Vittori Matteo , Antonucci Michele , Maiorino Francesco , Signoretti Marta , Petta Filomena , Travaglia Stefano , Panei Massimo , Bove Pierluigi 
Published: March 2023

ObjectivesTo evaluate the reliability of transperineal interstitial laser ablation of the prostate (TPLA) in preserving antegrade ejaculation compared to transurethral resection of the prostate (TURP).Patients and MethodsIn this single‐centre, prospective, randomized, open‐label study, consecutive patients with indication for surgical treatment for benign prostatic obstruction (BPO) were enrolled between January 2020 and September 2021 (NCT04781049). Patients were randomized to one of two treatment arms: Group A: TPLA (experimental group) and Group B: TURP (reference standard group). The primary endpoint was change in ejaculatory function (assessed by the Male Sexual Health Questionnaire – Ejaculatory function domain [EJ‐MSHQ]) at 1 month after surgery. Secondary endpoints included comparison of visual analogue scale (VAS) scores, changes in sexual function (assessed using the five‐item International Index of Erectile Function [IIEF‐5]), change in International Prostate Symptom Score [IPSS], change in quality of life score, and maximum urinary flow rate [Qmax] improvement at 1–6 months, as appropriate.ResultsFifty‐one patients (26 TPLA vs 25 TURP) were analysed. No differences in the perception of pain assessed by VAS and no differences in IIEF‐5 score were found between the groups. The distribution of ejaculatory function assessed by the EJ‐MSHQ remained unmodified after TPLA (P = 0.2), while a median 30% decrease in EJ‐MSHQ score was observed after TURP (P = 0.01). Absence of antegrade ejaculation was reported in one patient in the TPLA group (vs 18 patients in the TURP group). A statistically significant difference between the treatment groups was found in terms of postoperative Qmax (TPLA vs TURP: 15.2 [interquartile range 13.5–18.3] mL/s vs 26.0 [interquartile range 22.0–48.0] mL/s; P < 0.001). Both treatments significantly improved Qmax, with a mean 23.9 mL/s improvement after TURP (95% confidence interval [CI] 17.1–30.7) vs 6.0 mL/s after TPLA (95% CI 5.0–7.0), and IPSS, with a mean decrease of 11.6 (95% CI 9.7–13.5) vs 5.8 after TPLA (95% CI.2–9.6) with respect to baseline.ConclusionIn our study, TPLA preserved ejaculatory function in 96% of cases in addition to providing significant relief from BPO.
Chlorogenic acid reduces inflammation by inhibiting the elevated expression of KAT2A to ameliorate lipopolysaccharide‐induced acute lung injury
Authors: Lv Bin , Guo Jinhe , Du Yaodong , Chen Yang , Zhao Xin , Yu Bin , Liu Jiarui , Cui Tianyi , Mao Haoping , Wang Xiaoying , Gao Xiumei 
Published: March 2023

Background and PurposeRespiratory diseases have become a global health problem and may lead to acute lung injury (ALI) in severe cases. ALI progression is associated with complex pathological changes; however, there are currently no effective therapeutic drugs. Excessive activation and recruitment of immunocytes in the lungs and the release of large amounts of cytokines are considered the primary causes of ALI, but the cellular mechanisms involved remain unknown. Therefore, new therapeutic strategies need to be developed to control the inflammatory response and prevent the further aggravation of ALI.Experimental ApproachLipopolysaccharide was administered to mice via tail vein injection to establish an ALI model. Key genes regulating lung injury in mice were screened by RNA sequencing (RNA‐seq), and their regulatory effects on inflammation and lung injury were assessed in in vivo and in vitro experiments.Key ResultsThe key regulatory gene KAT2A up‐regulated the expression of inflammatory cytokines and induced lung epithelial injury. Chlorogenic acid, a small natural molecule and KAT2A inhibitor, inhibited the inflammatory response and significantly improved the decreased respiratory function caused by lipopolysaccharide administration in mice by inhibiting the expression of KAT2A.Conclusion and ImplicationsTargeted inhibition of KAT2A suppressed the release of inflammatory cytokines and improved respiratory function in this murine model of ALI. Chlorogenic acid, a specific KAT2A‐targeting inhibitor, was effective in treating ALI. In conclusion, our results provide a reference for the clinical treatment of ALI and contribute to the development of novel therapeutic drugs for lung injury.
Drainage area estimates for synorogenic clastic wedges in the Central Appalachian Basin (sink) with implications for terrane accretion in the hinterland (source)
Authors: Eriksson Kenneth A. , McClung Wilson S. , Simpson Edward L. 
Published: March 2023

AbstractSource‐to‐sink studies typically utilize the sedimentary record preserved in basins to infer source area parameters such as estimates of drainage area and discharges of fluvial systems in the hinterland, the characterization of which remains elusive as few geomorphic elements of the hinterland are preserved. Clastic wedges within foreland basin settings often contain fluvial deposits, and the scale of fluvial architectural elements can be used to estimate drainage area and discharge within the accreted hinterland. This study uses thicknesses of fluvial architectural elements within the Late Ordovician Taconic, the Late Devonian‐Early Mississippian Acadian, and the Late Mississippian to Early and Middle Pennsylvanian Alleghanian clastic wedges, together with climatic conditions interpreted from palaeosol data, to estimate the drainage areas and discharges of the river systems which drained the hinterlands of the accreted Taconic and Acadian terrains and the Alleghanian suture of Laurentia and Gondwana. Published detrital zircon age spectra provide insight into ages of source areas of sediments as well as the timing of terrane accretion. The increase in hinterland drainage areas calculated for Late Devonian Acadian Orogeny river systems compared to Late Ordovician Taconic Orogeny river systems can be attributed to the increase in size of accreted terranes to the east of the foreland basins during that period of time. The decrease in hinterland drainage area from the Late Devonian Acadian Orogeny to the Middle to Late Pennsylvanian Alleghanian Orogeny is attributed to the westward migration of the drainage divide as the Alleghanian orogeny proceeded. It is inferred that the drainage divide migrated towards the drier leeward side of the mountain range and caused drainage basins to shrink and split into smaller drainage basins.
TIP60 is required for tumorigenesis in non‐small cell lung cancer
Authors: Shibahara Daisuke , Akanuma Naoki , Kobayashi Ikei S. , Heo Eunyoung , Ando Mariko , Fujii Masanori , Jiang Feng , Prin P. Nicholas , Pan Gilbert , Wong Kwok‐Kin , Costa Daniel B. , Bararia Deepak , Tenen Daniel G. , Watanabe Hideo , Kobayashi Susumu S. 
Published: March 2023

AbstractHistone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development and maintenance, although its function in lung cancer remains controversial. Here we demonstrate that TIP60 knockdown in non‐small cell lung cancer cell lines decreased tumor cell growth, migration, and invasion. Furthermore, analysis of a mouse lung cancer model with lung‐specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA‐seq and ChIP‐seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. Investigation of a connectivity map database identified several candidate compounds that decrease TIP60 mRNA, one that suppressed tumor growth in cell culture and in vivo. In addition, TH1834, a TIP60 acetyltransferase inhibitor, showed comparable antitumor effects in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor‐specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach to treating lung cancer.
Diversity in verbal fluency performance and its associations with MRI‐informed brain age matrices in normal ageing and neurocognitive disorders
Authors: Lu Hanna , Li Jing , Fung Ada Wai Tung , Lam Linda Chiu Wa 
Published: March 2023

AbstractIntroductionCategory verbal fluency test (CVFT) has been widely used to assess and monitor the cognitive capacities in epidemiological studies and clinical trials. Pronounced discrepancy in CVFT performance has been found in individuals with different cognitive statuses. This study aimed to combine the psychometric and morphometric approaches to decode the complex verbal fluency performance in senior adults with normal ageing and neurocognitive disorders.MethodsThis study adopted a two‐stage cross‐sectional design involving quantitative analyses of neuropsychological and neuroimaging data. In study I, capacity‐ and speed‐based measures of CVFT were developed to evaluate the verbal fluency performance in normal ageing seniors (n = 261), those with mild cognitive impairment (n = 204), and those with dementia (n = 23) whose age range is from 65 to 85 years. In study II, structural magnetic resonance imaging‐informed gray matter volume (GMV) and brain age matrices were calculated in a subsample (n = 52) from Study I through surface‐based morphometry analysis. With age and gender as covariates, Pearson's correlation analysis was used to examine the associations of CVFT measures, GMV, and brain age matrices.ResultsSpeed‐based measures showed extensive and stronger associations with other cognitive functions than capacity‐based measures. The component‐specific CVFT measures showed shared and unique neural underpinnings with lateralized morphometric features. Moreover, the increased CVFT capacity was significantly correlated with younger brain age in mild neurocognitive disorder (NCD) patients.ConclusionWe found that the diversity of verbal fluency performance in normal ageing and NCD patients could be explained by a combination of memory, language, and executive abilities. The component‐specific measures and related lateralized morphometric correlates also highlight the underlying theoretical meaning of verbal fluency performance and its clinical utility in detecting and tracing the cognitive trajectory in individuals with accelerated ageing.
Indication for molecular testing by multiplex ligation‐dependent probe amplification in parkinsonism
Authors: Mutez E. , Swiderski M. , Devos D. , Moreau C. , Baille G. , Degardin A. , Ryckewaert G. , Carriere N. , Kreisler A. , Simonin C. , Rouaix N. , Tir M. , Krystkowiak P. , Ramdane N. , Génin M. , Sablonnière B. , Defebvre L. , Huin V. 
Published: March 2023

AbstractBackground and purposeThe monogenic forms of Parkinson's disease represent <10% of familial cases and a still lower frequency of sporadic cases. However, guidelines to orient genetic testing are lacking. The aim was to establish the interest of multiplex ligation‐dependent probe amplification (MLPA) as a primary screening test and to propose clinical criteria to guide genetic diagnostic tests for patients with suspected Mendelian Parkinson's disease.MethodsIn all, 567 patients with parkinsonism from 547 unrelated families were recruited and two MLPAs were performed for each. All pathogenic G2019S variants in the LRRK2 gene were confirmed by Sanger sequencing and the PRKN gene was screened for a second mutation in the cases of one heterozygous structural variant in the PRKN gene.ResultsThe performance of MLPA was 51/567 (9%) for the entire cohort and included 27 (4.8%) LRRK2 G2019S mutations, 19 (3.4%) PRKN mutations and five (0.9%) SNCA locus duplications. The variables significantly associated with a positive test in the total cohort were North African ancestry (p < 0.0001), female sex (p = 0.004) and younger age at onset (p < 0.0008).ConclusionsRetrospective analysis allowed us to refine our indication criteria: (i) North African ancestry, (ii) an age at onset <40 years or (iii) a familial history of parkinsonism with at least one affected first‐degree relative. Our study highlights the interest of MLPA testing for other parkinsonism cases with a family history, especially for patients with dementia with Lewy bodies or a multiple‐system‐atrophy‐like phenotype.