bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax combined chemotherapy versus chemotherapy alone for acute myeloid leukemia: a systematic review and meta-analysis
Authors: Zhu Jingkui , Fan Jixin , Xie Tiantian , Zhao Haiqiu , Lu Runqing , Zhang Yinyin , Li Yingmei , Xie Xinsheng , Wan Dingming , Jiang Zhongxing , He Fei , Guo Rong 
Published: March 2024

ObjectiveTo compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML).MethodTo compare the efficacy and/or safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs).ResultA total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group.ConclusionThe VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288, identifier CRD42023439288.
Sacituzumab Govitecan for the treatment of advanced triple negative breast cancer patients: a multi-center real-world analysis
Authors: Caputo Roberta , Buono Giuseppe , Piezzo Michela , Martinelli Claudia , Cianniello Daniela , Rizzo Alessandro , Pantano Francesco , Staropoli Nicoletta , Cangiano Rodolfo , Turano Salvatore , Paris Ida , Nuzzo Francesco , Fabi Alessandra , De Laurentiis Michelino 
Published: March 2024

ObjectiveThe objective of this multicenter, observational, retrospective analysis was to evaluate the safety and efficacy of sacituzumab govitecan in metastatic triple-negative breast cancer (mTNBC) patients managed according to common clinical practice in Italy.MethodsData were retrieved by 7 sites. Triple-negative BC was defined by the lack of expression of estrogen receptor (ER &lt;1%), progesterone receptor (PgR &lt;1%) and human-epidermal growth factor receptor-2 (HER2 0, 1+, 2+ ISH-not amplified) according to standard ASCO-CAP criteria. Demographic and clinical characteristics were collected. Premedication, dose modifications and treatment schedule were based on the approved label of the product. Adverse events (AEs) were assessed according to NCI-CTCAE v5.0.ResultsFifty-seven eligible patients who received sacituzumab govitecan for mTNBC were included. Median age was 53 years (range 25-75). Approximately 70% of patients had an initial diagnosis of TNBC. Median time from the diagnosis of metastatic BC to start of sacituzumab govitecan was 17 months (range 0-97) and median number of previous therapies was 3 (range 1-7). The most common sites of metastasis were lymph nodes (63.1% of patients), lung (57.9%), bone (50.8%) and liver (38.6%). Eight (14.0%) patients had a disease-free interval ≤12 months. A total of 32 (56.1%) deaths were observed and the median overall survival (OS) was 12.43 months (95% CI, 7.97 months-not reached). At a median follow-up of 10.6 months, 45 patients (78.9%) had progression and the median progression-free survival (PFS) was 4.9 months (95% CI, 3.7-7.1 months). Partial tumour response was observed in 19 patients (33.3%), stable disease in 16 (28.1%) and disease progression in 22 patients (38.6%). The most common treatment-related AEs were anemia (66.6% of patients), alopecia (66.6%), neutropenia (59.6%), nausea (42.1%) and diarrhea (38.6%). Neutropenia was the most common serious treatment-related AE: 21.0% and 8.7% of patients experienced grade 3 or 4 neutropenia, respectively. Twenty-two patients (38.6%) reduced the dose and 5.3% permanently discontinued treatment.ConclusionThe results of this real-world analysis showed that both safety and efficacy of sacituzumab govitecan in mTNBC patients are consistent with that previously reported in regulatory trials. The use of premedication and supportive measures was associated with a satisfactory toxicity profile.
Dosing optimization of rituximab for primary membranous nephropathy by population pharmacokinetic and pharmacodynamic study
Authors: Liang Hao , Deng Zhenling , Niu Shu , Kong Weijie , Liu Yang , Wang Song , Li Haiyan , Wang Yue , Zheng Danxia , Liu Dongyang 
Published: March 2024

Primary membranous nephropathy (PMN) is the most common cause for adult nephrotic syndrome. Rituximab has demonstrated promising clinical efficacy by random controlled trials and the off-label use is widely adopted in PMN. However, the standard dosage is borrowed from B cell lymphoma treatment with far more antigens and is oversaturated for PMN treatment, accompanied with additional safety risk and unnecessary medical cost. More than 15% serious adverse events were observed under standard dosage and low dose therapies were explored recently. Dose optimization by clinical trials is extremely time- and cost-consuming and can be significantly accelerated with the aid of model-informed drug development. Here, we aim to establish the first population pharmacokinetic and pharmacodynamic (PPK/PD) model for rituximab in PMN to guide its dosage optimization. Rituximab pharmacokinetic and pharmacodynamic data from 41 PMN patients in a retrospective study under a newly proposed monthly mini-dose were used to construct quantitative dose-exposure-response relationship via mechanistic target-mediated drug disposition (TMDD) model followed by regression between the reduction of anti-PLA2R titer and time after the treatment. The final model, validated by goodness-of-fit plots, visual predictive checks and bootstrap, was used to recommend the optimized dosing regimen by simulations. The model was well validated for PK/PD prediction. The systemic clearance and half-life are 0.54 L/h and 14.7 days, respectively. Simulation of a novel regimen (6 monthly doses of 100 mg) indicated the comparable ability and superior duration time of CD20+ B cell depletion compared with standard dosage, while the cumulative dosage and safety risk was significantly decreased. We established the first PPK/PD model and provide evidence to support the dosage optimization based on monthly mini-dose. Our study can also efficiently accelerate dosage optimization of novel anti-CD20 antibodies in PMN and other indications.
Design and synthesis of novel dihydropyridine- and benzylideneimine-based tyrosinase inhibitors
Authors: Ahmad Ifraz , Parveen Warda , Noor Shah , Udin Zahoor , Ali Amjad , Ali Ijaz , Ullah Riaz , Ali Hamid 
Published: March 2024

Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine (4). The novel conjugates 6 (a–o) were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy. The purified compound 4 was refluxed with various aldehydes and ketones 5 (a–o) for 5–8 h in methanol at 60°C–90°C. This research modified the drug in a step-by-step manner to develop therapeutic properties as a tyrosinase inhibitor. The structures of synthesized ligands 6 (a–o) were established based on spectral and analytical data. The synthesized compounds 6 (a–o) were screened against tyrosinase enzyme. Kojic acid was taken as standard. All the prepared compounds 6 (a–o) have good inhibition potential against the enzyme tyrosinase. Compounds 6o, 6b, 6f, and 6k depicted excellent antityrosinase activity. Compound 6k, with an IC50 value of 5.34 ± 0.58 µM, is as potent as the standard kojic acid (IC50 6.04 ± 0.11 µM), standing out among all synthesized compounds 6 (a–o). The in silico studies of the conjugates 6 (a–o) were evaluated via PatchDock. Compound 6k showed a binding affinity score of 8,999 and an atomic contact energy (ACE) value of −219.66 kcal/mol. The structure–activity relationship illustrated that the presence of dihydropyridine nuclei and some activating groups at the ortho and para positions of the benzylideneimine moiety is the main factor for good tyrosinase activity. The compound 6k could be used as a lead compound for drug modification as a tyrosinase inhibitor for skin care, anticancer medication, and antibrowning for fruits and vegetables.
Inhibition of ACOX1 enhances the therapeutic efficacy of obeticholic acid in treating non-alcoholic fatty liver disease and mitigates its lipotoxicity
Authors: Yang Yuping , Yuan Weinan , He Kun , Lin Chuangzhen , Du Shenshen , Kou Yanqi , Nie Biao 
Published: March 2024

Background and aims:High-dose Obeticholic acid exhibits promise for non-alcoholic fatty liver disease (NAFLD) treatment but can induce lipotoxicity. Our study sought to understand this mechanism and propose a solution.Approach and Results:In a non-alcoholic fatty liver disease (NAFLD) model induced by a high-fat diet in FXR−/− mice, we pinpointed that FXR regulated the expression of ACOX1 through RNA-Seq analysis. In the livers of FXR−/− mice, both ACOX1 mRNA and protein expression notably decreased. In both HL-7702 and HEP-G2 cells, the silencing of FXR through shRNA plasmids decreased ACOX1 expression, while FXR activation with GW4064 increased it. These effects were reversible with the ACOX1-specific inhibitor, 10,12-Tricosadiynoic acid. In the NAFLD model of FXR−/− mice, The activation of ACOX1 is correlated with elevated serum LDL, triglycerides, and aggravated hepatic steatosis. However, the combination of 10,12-Tricosadiynoic acid with low-dose obeticholic acid effectively treated hepatic steatosis, reducing LDL levels in the NAFLD model of wild-type mice. This combination therapy demonstrated efficacy comparable to high-dose obeticholic acid alone. Notably, the combined drug regimen treats hepatic steatosis by inhibiting the IL-1β and α-SMA pathways in NAFLD.Conclusion:Combining ACOX1-specific inhibitors with low-dose obeticholic acid effectively treats high-fat diet-induced hepatic steatosis and reduces serum LDL. This approach enhances the therapeutic effects of obeticholic acid and mitigates its lipotoxicity by inhibiting the IL-1β and α-SMA pathways.
The fairness of human resource management practices: an assessment by the justice sensitive
Authors: Haines Victor Y. , Patient David , Guerrero Sylvie 
Published: March 2024

IntroductionAlthough fairness is a pervasive and ongoing concern in organizations, the fairness of human resource management practices is often overlooked. This study examines how individual differences in justice sensitivity influence the extent to which human resource management practices are perceived to convey principles of organizational justice.MethodsAnalysis was performed on a matching sample of 283 university students from three academic units in two countries having responded at two time points. Justice sensitivity was measured with the 40-item inventory developed and validated by Schmitt et al. (2010). Respondents were instructed to indicate to what extent each of 61 human resource management practices generally conveys principles of organizational justice.ResultsJustice sensitivity was positively associated with subsequent assessments of the justice contents of human resource management practices. The distinction between self-oriented and other-oriented justice sensitivities was helpful in determining perceptions of these human resource management practices and of a subset of pay-for-performance practices.DiscussionThe findings inform current research about the meanings borne by human resource management practices, and also increase understanding of entity judgment formation as an important aspect of systemic justice.
“FREED instils a bit of hope in the eating disorder community… that things can change.”: an investigation of clinician views on implementation facilitators and challenges from the rapid scaling of the First Episode Rapid Early Intervention for Eating Disorders programme
Authors: Hyam Lucy , Yeadon-Ray Olivia , Richards Katie , Semple Amy , Allen Karina , Owens Jill , Jackson Aileen , Semple Laura , Glennon Danielle , Di Clemente Giulia , Griffiths Jess , Mills Regan , Schmidt Ulrike 
Published: March 2024

IntroductionFirst Episode Rapid Early Intervention for Eating Disorders (FREED) is the leading eating disorder (ED) early intervention model for young people. Research has shown that it reduces the duration of untreated illness, improves clinical outcomes, and has cost savings. However, less is known about the experience of implementing FREED. This study aimed to investigate the views and experiences of adopting, implementing, and sustaining FREED from the perspective of clinical staff.MethodsSeven focus groups were conducted involving 26 clinicians. Thematic analysis was used, with the Non-Adoption, Abandonment and Challenges to Scale-up, Spread and Sustainability (The NASSS framework) framework being applied to organise subthemes and determine facilitators and barriers. The NASSS framework was also used to rate the complexity of themes as either simple (straightforward, predictable, few components), complicated (multiple interrelating components), or complex (dynamic, unpredictable, not easily divisible into constituent components).ResultsThere were 16 subthemes identified under seven broader themes representing each domain of the NASSS framework. Key barriers and areas of complexity included factors related to EDs as an illness (e.g., high acuity and prevalence), and organisational complexity (e.g., staffing shortages, lack of managerial/team support). Key facilitators included positive clinician/adopter attitudes, a supportive national network, and the ability for FREED to be flexible/adaptable over time.ConclusionThe FREED model appears to be desirable to clinical staff. Wider team and managerial support was perceived to be particularly important to its successful implementation, as were the national network and supervision. Key areas of complexity include staffing issues and high ED acuity/prevalence. These barriers to implementation need to be managed and investment continued to expand and improve early intervention for EDs further.
Challenges for palliative care in times of COVID-19: a scoping review
Authors: Lourenço Marisa , Gomes Tânia , Araujo Fátima , Ventura Filipa , Silva Rosa 
Published: March 2024

IntroductionMany of the essential practices in palliative care (PC) had to be adapted to the COVID-19 pandemic. This global spread of the infectious respiratory disease, caused by SARS-CoV-2, created unprecedented obstacles. The aim of this research was to comprehensively assess the experiences and perceptions of healthcare professionals, individuals, and families in palliative and end-of-life situations during the COVID-19 pandemic.MethodsA scoping review was conducted using the databases CINAHL Complete, MEDLINE, Scopus, SciELO, Cochrane Central Register of Controlled Trials, Psychology and Behavioral Sciences, MEDIClatina, and Portugal’s Open Access Scientific Repository. The review followed the JBI® methodological approach for scoping reviews.ResultsOut of the initially identified 999 articles, 22 studies were included for analysis. The deprivation of relationships due to the safety protocols required to control the spread of COVID-19 was a universally perceived experience by healthcare professionals, individuals in PC, and their families. Social isolation, with significant psychological impact, including depersonalization and despair, was among the most frequently reported experiences by individuals in palliative situation. Despite healthcare professionals’ efforts to mitigate the lack of relationships, the families of these individuals emphasized the irreplaceability of in-person bedside contact.Systematic review registrationhttps://osf.io/xmpf2/.
Transplantation of a free fillet flap from discarded fingers for repair of a finger pulp skin defect: a case report
Authors: Zhou Xianting , Zhang Chenxi , Fan Xuekai , Cai Xiaoming , Wang Xin , Pan Jiadong 
Published: March 2024

BackgroundReplantation represents a treatment option for patients with severed finger pulps. However, in some cases, replantation is a challenging task.Case presentationWe report a successful case of finger pulp reconstruction of the ring finger using free flaps from a nonreplantable index finger in a spare-parts procedure. A 43-year-old worker accidentally injured the index, middle and ring fingers of his left hand on a machine turntable. The severed index and middle fingers and the distal pulp of the ring finger could not be replanted in situ due to extensive contusion of blood vessels and soft tissues. After vascular and nerve anastomosis, a free skin flap isolated from the nonreplantable index finger was transplanted to the wound of the distal pulpal defect of the ring finger. The flap survived completely postoperatively. Six months after the operation, only a slight deformity of the ring finger was observed. Moreover, sensation of the digit recovered well.ConclusionsSpare-part surgery is a surgical approach that effectively saves and utilizes tissue that would otherwise be discarded in cases of severe limb trauma. This idea may be applied to treatment of severe injuries to multiple fingers. Additionally, in the process of tissue transplantation and repair, attention should be given to protecting the tissue in the recipient area to avoid damage to the original undamaged tissue structure, which can adversely affect healing and recovery of the tissue.
Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19
Authors: Boland Lidvine , Devresse Arnaud , Monchaud Caroline , Briol Sébastien , Belaiche Stéphanie , Giguet Baptiste , Couzi Lionel , Thaunat Olivier , Esposito Laure , Meszaros Magdalena , Roussoulieres Ana , Haufroid Vincent , Le Meur Yannick , Lemaitre Florian 
Published: March 2024

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.
PENGARUH POSISI JONGKOK PADA KALA II PERSALINAN
Authors: Yuniah Yuyun , Indrayani Diyan 
Published: March 2024

Posisi persalinan dapat meningkatkan kenyamanan dengan merangsang reseptor di otak yang menurunkan persepsi nyeri akibat kontraksi uterus sehingga hal ini dapat mempercepat persalinan. Posisi persalinan dapat membantu bayi bergerak melalui panggul, dan beberapa posisi memperbesar diameter panggul. Bidan mempunyai peran penting dalam memberi dukungan dan memfasilitasi ibu memilih posisi persalinan yang nyaman dan tepat sehingga dapat mempersingkat lama persalinan. Posisi jongkok merupakan salah satu alternatif posisi persalinan yang bermanfaat memperpendek lama kala II persalinan. Posisi jongkok termasuk kategori posisi tegak sehingga memberi gaya gravitasi yang membantu mendorong bagian terendah janin turun, meningkatkan diameter panggul sehingga membantu rotasi janin serta ibu bebas bergerak mengendalikan berat badannya sehingga terasa nyaman. Laporan kasus berbasis bukti ini bertujuan untuk mengetahui pengaruh posisi jongkok pada kala II persalinan pada primipara di UPT Puskemas Padasuka. Penelusuran artikel mengenai perbandingan posisi persalinan ini melalui Google scholar, Pubmed dan Chocrane Library dengan strategi kata kunci pencarian birth position OR squatting position AND duration second stage of labor. Didapatkan 2 artikel yang sesuai dengan kriteria inklusi dan eksklusi dan telah dilakukan penapisan sebelumnya, kemudian ditelaah secara kritis. Setelah ditelaah secara kritis dari kedua artikel dinyatakan penting dan dapat diterapkan kepada pasien. Posisi jongkok dilakukan oleh ibu primipara pada kala II persalinan. Diperoleh hasil bahwa lama persalinan kala II 13 menit dengan demikian posisi jongkok dalam kala II persalinan efektif dalam mempercepat persalinan.
EVIDANCE BASED CASED REPORT (EBCR) : PENGARUH PEMERAHAN TALI PUSAT TERHADAP KADAR HEMOGLOBIN PADA BAYI BARU LAHIR
Authors: Novela Septi Eka , Legiati P. S. Titi 
Published: March 2024

Latar Belakang: Penjepitan dan pemotongan tali pusat merupakan bagian dari manajemen Asuhan Persalinan Normal (APN) yang termasuk dalam manajemen aktif kala III. Pemotongan tali pusat segera menyebabkan tidak terjadinya penambahan volume darah sehingga tranfusi plasenta akan mengalami kehilangan 33% zat besi. Kehilangan zat besi menyebabkan bayi beresiko mangalami anemia selama 0-4 bulan. Pemerahan tali pusat menjadi salah satu alternatif yang bertujuan memberikan tranfusi plasenta pada bayi secara optimal sehingga dapat mengurangi resiko anemia pada bayi. Tujuan: Evidence based case report ini bertujuan untuk mengetahui pengaruh pemerahan tali pusat terhadap kadar hemoglobin pada bayi baru lahir. Metode: Penelusuran artikel mengenai pengaruh pemerahan tali pusat terhadap kadar hemoglobin pada bayi baru lahir dilakukan melalui database Pubmed dan Cochrane. Didapatkan 2 artikel oleh Kilicdag dkk dan Jeevan dkk yang sesuai dengan kriteria inklusi dan ekslusi yang kemudian ditelaah secara kritis. Hasil: Hasil pengukuran kadar

hemoglobin pada bayi yang menerima intervensi saat berusia 38 jam yaitu sebesar 23,8 gr/dL. Hal ini menunjukan bahwa bayi yang menerima intervensi pemerahan tali pusat memiliki kadar hemoglobin lebih tinggi dibandingkan dengan bayi tanpa pemerahan tali pusat. Simpulan: Pemerahan tali pusat terbukti sebagai strategi yang tepat dalam meningkatkan kadar hemoglobin pada bayi baru lahir.