bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salivary gland organoid transplantation as a therapeutic option for radiation-induced xerostomia
Authors: Jeon Seong Gyeong , Lee Jaeseon , Lee Su Jeong , Seo Jaehwi , Choi Jinkyoung , Bae Dong Hyuck , Chun Duk-Hee , Ko Seung Young , Shin Hyun Soo , Joo Lina , Lee Sang-Hyuk , Lim Young Chang , Choi Woo Hee , Yoo Jongman 
Published: August 2024

Abstract
Background
Xerostomia is a pathological condition characterized by decreased salivation due to salivary gland dysfunction and is frequently attributed to irreversible damage as a side effect of radiation therapy. Stem cell–derived organoid therapy has garnered attention as a promising avenue for resolving this issue. However, Matrigel, a hydrogel commonly used in organoid culture, is considered inappropriate for clinical use due to its undefined composition and immunogenicity. In this study, we aimed to develop a method for culturing collagen-based human salivary gland organoids (hSGOs) suitable for clinical applications and evaluated their therapeutic effectiveness.

Methods
Human salivary gland stem cells were isolated from the salivary gland tissues and cultured in both Matrigel and collagen. We compared the gene and protein expression patterns of salivary gland–specific markers and measured amylase activity in the two types of hSGOs. To evaluate the therapeutic effects, we performed xenogeneic and allogeneic transplantation using human and mouse salivary gland organoids (hSGOs and mSGOs), respectively, in a mouse model of radiation-induced xerostomia.

Results
hSGOs cultured in Matrigel exhibited self-renewal capacity and differentiated into acinar and ductal cell lineages. In collagen, they maintained a comparable self-renewal ability and more closely replicated the characteristics of salivary gland tissue following differentiation. Upon xenotransplantation of collagen-based hSGOs, we observed engraftment, which was verified by detecting human-specific nucleoli and E-cadherin expression. The expression of mucins, especially MUC5B, within the transplanted hSGOs suggested a potential improvement in the salivary composition. Moreover, the allograft procedure using mSGOs led to increased salivation, validating the efficacy of our approach.

Conclusions
This study showed that collagen-based hSGOs can be used appropriately in clinical settings and demonstrated the effectiveness of an allograft procedure. Our research has laid the groundwork for the future application of collagen-based hSGOs in allogeneic clinical trials.
KCNJ16-depleted kidney organoids recapitulate tubulopathy and lipid recovery upon statins treatment
Authors: Sendino Garví E. , van Slobbe G. J. J. , Zaal E. A. , de Baaij J. H. F. , Hoenderop J. G. , Masereeuw R. , Janssen M. J. , van Genderen A. M. 
Published: August 2024

Abstract
Background
The KCNJ16 gene has been associated with a novel kidney tubulopathy phenotype, viz. disturbed acid–base homeostasis, hypokalemia and altered renal salt transport. KCNJ16 encodes for Kir5.1, which together with Kir4.1 constitutes a potassium channel located at kidney tubular cell basolateral membranes. Preclinical studies provided mechanistic links between Kir5.1 and tubulopathy, however, the disease pathology remains poorly understood. Here, we aimed at generating and characterizing a novel advanced in vitro human kidney model that recapitulates the disease phenotype to investigate further the pathophysiological mechanisms underlying the tubulopathy and potential therapeutic interventions.

Methods
We used CRISPR/Cas9 to generate KCNJ16 mutant (KCNJ16+/− and KCNJ16−/−) cell lines from healthy human induced pluripotent stem cells (iPSC) KCNJ16 control (KCNJ16WT). The iPSCs were differentiated following an optimized protocol into kidney organoids in an air–liquid interface.

Results
KCNJ16-depleted kidney organoids showed transcriptomic and potential functional impairment of key voltage-dependent electrolyte and water-balance transporters. We observed cysts formation, lipid droplet accumulation and fibrosis upon Kir5.1 function loss. Furthermore, a large scale, glutamine tracer flux metabolomics analysis demonstrated that KCNJ16−/− organoids display TCA cycle and lipid metabolism impairments. Drug screening revealed that treatment with statins, particularly the combination of simvastatin and C75, prevented lipid droplet accumulation and collagen-I deposition in KCNJ16−/− kidney organoids.

Conclusions
Mature kidney organoids represent a relevant in vitro model for investigating the function of Kir5.1. We discovered novel molecular targets for this genetic tubulopathy and identified statins as a potential therapeutic strategy for KCNJ16 defects in the kidney.
Oncological characteristics, treatments and prognostic outcomes in MMR-deficient colorectal cancer
Authors: Fan Wen-Xuan , Su Fei , Zhang Yan , Zhang Xiao-Ling , Du Yun-Yi , Gao Yang-Jun , Li Wei-Ling , Hu Wen-Qing , Zhao Jun 
Published: August 2024

AbstractColorectal cancer (CRC) ranks as the third most prevalent cancer globally. It’s recognized that the molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines the current molecular classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic cases. Despite advances in understanding of these genetic backgrounds, clinical trials have not conclusively differentiated the efficacy of immune checkpoint inhibitors among these subgroups. Therefore, while this review details the molecular characteristics and their general implications for treatment and prognosis, it also highlights the limitations and the need for more refined clinical studies to ascertain tailored therapeutic strategies for each subtype. Furthermore, this review summarizes completed and ongoing clinical studies, emphasizing the importance of developing treatments aligned more closely with molecular profiles. By discussing these aspects, the review seeks to provide a comprehensive analysis of oncological characteristics, presenting a detailed understanding of their implications for treatment and prognosis in dMMR/MSI-H CRC.
Comparative long-term outcomes of vitrectomy combined with anterior chamber intraocular lens to intra-scleral haptic fixation of posterior chamber intraocular lens
Authors: Warren Alexis , Kemp Pavlina S. , Coussa Razek G. , Cheng Liang , Boldt H. Culver , Russell Stephen R. , Johnson A. Tim , Oetting Thomas A. , Sohn Elliott H. 
Published: August 2024

Abstract
Purpose
To evaluate the long-term clinical outcomes in patients with combined pars plana vitrectomy (PPV) with anterior chamber intraocular lens (ACIOL) to intrascleral haptic fixation (ISHF) using the Agarwal technique with fibrin glue to secure the scleral flap of a posterior chamber intraocular lens.

Methods
Retrospective, consecutive, single-center, comparative case series. 83 eyes were studied. Patients with < 8 months of follow-up were excluded. Detailed pre-, intra-, and post-operative complications were analyzed using mixed model univariate analysis and t-test. Pre- and post-operative best corrected visual acuity (BCVA) was analyzed.

Results
Twenty-five subjects met entry criteria. Mean age at time of surgery was 70.4 ± 17.7 years in the ACIOL group (n = 12) and 54.6 ± 21.1 years in the ISHF group (n = 13; p = 0.03). Mean follow-up was 38.2 months. Incidence of corneal decompensation was similar in the ACIOL and ISHF lens group (p = 0.93). There was no difference in the BCVA mean change or cystoid macular edema (CME) at the final visit between the groups (p = 0.47; p = 0.08), but there was a trend toward increased CME in the ACIOL group.

Conclusions
PPV with concomitant placement of either ACIOL or ISHF lens result in improvement in BCVA. Both procedures are well tolerated and result in favorable outcomes with long-term follow-up though varying patient populations do not allow precise comparison between the two groups.
Non-invasive hemodynamic monitoring during initiation of positive airway pressure treatment in patients with obstructive sleep apnea: a feasibility study
Authors: Müller Christoph , Kerl Jens , Dellweg Dominic 
Published: August 2024

Abstract
Background
The association of obstructive sleep apnea (OSA) with cardiovascular morbidity has been repeatedly reported in numerous studies and argues for treatment initiation even in the absence of significant day time sleepiness. While the long-term consequences of positive airway pressure (PAP) treatment on OSA related comorbidities like secondary hypertension are based on substantial clinical evidence, less is known about the immediate hemodynamic effects.

Methods
This study tried to investigate the impact of PAP treatment on different hemodynamic parameters in 48 patients with OSA by extending the standard polysomnographic assessment with non-invasive hemodynamic monitoring using impedance cardiography (ICG). On two consecutive nights under diagnostic and therapeutic conditions, polysomnographic and hemodynamic data were acquired. In addition, we subdivided the participants according to their treatment related change in stroke volume (SV) and assigned the hemodynamic measurements to the corresponding sleep stage.

Results
Comparing both conditions, a non-statistically significant decrease in SV and cardiac output (CO) was observed for all participants. Treatment initiation was associated with a statistically significant prolongation of the pre-ejection period (PEP) for the entire study population (p = 0.001) and the subgroup with decreasing SV (p = 0.008). In addition, systolic blood pressure (SBP) (p = 0.026) and pulse pressure (PP) (p = 0.041) were lowered significantly for patients with a therapeutically reduced SV under treatment conditions. A higher BMI (p = 0.020) and a more pronounced reduction of the respiratory distress index (RDI) (p = 0.030) and the arousal-index (p = 0.021) were observed for patients with decreasing SV. Correlational analysis revealed a negative relationship between the diagnostic values for both SBP (r=-0.324, p = 0.025) and PP (r=-0.407, p = 0.004) with the change in SV and a positive correlation with the change of the SBP (r = 0.317, p = 0.028) for all participants.

Conclusions
To conclude, our results indicate that treatment with a PAP device in patients with OSA can lead to a decrease in SV which is associated with a lowering of the SBP. This may be caused by a reduced sympathetic tone due to less respiratory events and an improved sleep profile.
Protective effect of β-sitosterol against high-fructose diet-induced oxidative stress, and hepatorenal derangements in growing female sprague-dawley rats
Authors: Gumede Nontobeko M. , Lembede Busisani W. , Nkomozepi Pilani , Brooksbank Richard L. , Erlwanger Kennedy H. , Chivandi Eliton 
Published: August 2024

Abstract
Background
Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed.

Results
High fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman’s capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function.

Conclusions
β-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.
TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy
Authors: Petrylak Daniel P. , Tagawa Scott T. , Jain Rohit K. , Bupathi Manojkumar , Balar Arjun , Kalebasty Arash Rezazadeh , George Saby , Palmbos Phillip , Nordquist Luke , Davis Nancy , Ramamurthy Chethan , Sternberg Cora N. , Loriot Yohann , Agarwal Neeraj , Park Chandler , Tonelli Julia , Vance Morganna , Zhou Huafeng , Grivas Petros , Petrylak Daniel P. , Tagawa Scott T. , Jain Rohit K. , Bupathi Manojkumar , Balar Arjun , Kalebasty Arash Rezazadeh , George Saby , Palmbos Phillip , Nordquist Luke , Davis Nancy , Ramamurthy Chethan , Sternberg Cora N. , Agarwal Neeraj , Park Chandler , Tonelli Julia , Vance Morganna , Zhou Huafeng , Grivas Petros , Loriot Yohann 
Published: August 2024

PURPOSE
Sacituzumab govitecan (SG) is a Trop-2–directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced (LA) or metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report results from Cohort 2 of TROPHY-U-01 trial, evaluating the efficacy and safety of SG in patients with mUC.

METHODS

TROPHY-U-01 (ClinicalTrials.gov identifier:
NCT03547973
) is a multicohort, open-label phase II study. Cohort 2 includes patients with LA or mUC who have had progression or recurrence after a CPI and were cisplatin-ineligible at study initiation. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end point was objective response rate (ORR) per central review; secondary end points were clinical benefit rate (CBR), duration of response (DOR), and progression-free survival (PFS) per central review and safety.

RESULTS
Cohort 2 included 38 patients (61% male; median age 72.5 years; 66% visceral metastases [29% liver]; 50% received previous PT-based chemotherapy as previous [neo]adjuvant therapy]). At a median follow-up of 9.3 months, ORR was 32% (95% CI, 17.5 to 48.7), CBR 42% (95% CI, 26.3 to 59.2), median DOR 5.6 months (95% CI, 2.8 to 13.3), median PFS 5.6 months (95% CI, 4.1 to 8.3), and median overall survival 13.5 months (95% CI, 7.6 to 15.6). Grade ≥3 treatment-emergent adverse events occurred in 87% of patients, most commonly neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), and diarrhea (16%).

CONCLUSION
SG monotherapy demonstrated a relatively high ORR with rapid responses; this was feasible with a manageable toxicity profile in cisplatin-ineligible patients who had progression after CPI therapy. Limitations include a moderate sample size and lack of random assignment. These results warrant further evaluation of SG alone and in combinations in patients with LA/mUC.
Identity Disclosure and Anthropomorphism in Voice Chatbot Design: A Field Experiment
Authors: Xu Yuqian , Dai Hongyan , Yan Wanfeng 
Published: August 2024

Fueled by the widespread adoption of algorithms and artificial intelligence, the use of chatbots has become increasingly popular in various business contexts. In this paper, we study how to effectively and appropriately use voice chatbots, particularly by leveraging the two design features identity disclosure and anthropomorphism, and evaluate their impact on the firm operational performance. In collaboration with a large truck-sharing platform, we conducted a field experiment that randomly assigned 11,000 truck drivers to receive outbound calls from the voice chatbot dispatcher of our focal platform. Our empirical results suggest that disclosing the identity of the chatbot at the beginning of the conversation negatively affects operational performance, leading to around 11% reduction in the response probability. However, humanizing the voice chatbot by adding our proposed anthropomorphism features (i.e., interjections and filler words) significantly improves response probability, conversation length, and the probability of order acceptance intention by over 5.6%, 24.9%, and 10.1%, respectively. Moreover, even when the chatbot’s identity is disclosed along with humanizing features, the operational outcomes still improve. This finding suggests that enhancing anthropomorphism may potentially counteract the negative effects of chatbot identity disclosure. Finally, we propose one plausible explanation for the performance improvement—the enhanced trust between humans and algorithms—and provide empirical evidence that drivers are more likely to disclose information to chatbot dispatchers with anthropomorphism features. Our proposed anthropomorphism improvement solutions are currently being implemented and utilized by our collaborator platform.This paper has been This paper was accepted by Felipe Caro for the Special Issue on the Human-Algorithm Connection.Funding: This study is supported by the National Natural Science Foundation of China [Grants 72172169 and 91646125], Program for Innovation Research at the Central University of Finance and Economic, and Shanghai Pujiang Program.Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.03833 .
Treating Employees With Dignity, Respect, and Fairness: The Impact on the Quality of Life of People With Intellectual and Developmental Disabilities
Authors: Friedman Carli , Gilden Cory 
Published: August 2024

Abstract
This study examined the impact of human service providers treating their employees with dignity, respect, and fairness on the quality of life of people with intellectual and developmental disabilities (IDD). We analyzed Personal Outcome Measures (n = 3,898 people with IDD) and Basic Assurances (n = 387 providers) data using multilevel logistic regressions. When providers treated their employees with dignity and respect, people with IDD were more likely to have the following outcomes present: health; continuity and security; realize goals; free from abuse and neglect; respect; decide when to share information; housing choice; fair treatment; rights; and choose services. How organizations treat their employees not only affects those employees, but also impacts the quality of life of people with IDD.
Vocational Calling, Meaningful Work, and Job Satisfaction Among Disability Services Providers
Authors: Carter Erik W. , Lanchak Emily R. , Morgan Grant B. 
Published: August 2024

Abstract
Recruiting and retaining a strong disability workforce remains an enduring concern in the field of intellectual and developmental disabilities. Yet little attention has focused on the sense of calling that disability service providers have to this important work and its relationships to their job satisfaction. We surveyed 269 disability service providers to examine whether they (a) perceive a calling in their life, (b) are living out that calling in their current work, (c) find meaning in their career, and (d) experience job satisfaction. The experience of both having and living out one’s calling in their current work was especially prominent among participants. Likewise, most providers indicated they drew considerable meaning and purpose from their work. Perceiving a calling contributed to higher job satisfaction through living out one’s calling and finding meaning in one’s work. Some variations in ratings were associated with personal demographics (i.e., sex, years of experience). These findings provide new insights into what might draw disability service providers into this work or sustain their commitment amidst challenging and changing working conditions. We highlight areas for research and practice aimed at place of calling within efforts to strengthening recruitment and retention.
Prevalence and factors associated with moderate-to-severe anaemia among virally suppressed people with HIV at a tertiary hospital in Zambia
Authors: Kamvuma Kingsley , Masenga Sepiso , Hamooya Benson , Chanda Warren , Munsaka Sody 
Published: August 2024

Objective
Anaemia is associated with an increased risk of disease progression and all-cause mortality among HIV-infected individuals, regardless of the type of anaemia, but the magnitude of the risk is greater with more severe forms of anaemia. Although anaemia PLWH has been extensively studied, the focus has primarily been on its prevalence and association with disease progression in untreated or poorly controlled HIV cases. This study aimed to investigate the prevalence, and factors associated with moderate-to-severe anaemia among virally suppressed HIV patients at a tertiary hospital in Zambia.

Methods
We conducted a cross-sectional study of ART-treated PLWH for at least 6 months at Livingstone University Teaching Hospital (LUTH). Sociodemographic, clinical, and laboratory were the data collected. The primary outcome moderate to severe anaemia was defined as follows; moderate anemia as haemaoglobin levels between 8.0–10.9 g/ and severe anemia as haemoglobin levels less than 8.0 g/dL according to the WHO classification. Logistic regression was performed to identify factors associated with moderate-to-severe anaemia.

Results
Among 823 participants with viral suppression, the overall prevalence of anaemia and moderate-to-severe anaemia was 29.4% (n = 242; 95% confidence interval (CI): 26.3–32.6) and 14.2% (n = 117, 95% CI: 11.7–18), respectively. In the adjusted logistic regression analysis, women had higher odds of moderate to severe anaemia compared to men (AOR 2.618, 95% CI 1.182–5.799). Lymphocyte count (AOR 0.525, 95% CI 0.31–0.90) and higher BMI (AOR 1.0671, 95% CI 1.01–1.13) were also significant factors. Microcytosis (AOR 49.79, 95% CI 12.95–191.49) and normocytosis (AOR 4.38, 95% CI 1.22–15.75) were strongly associated with higher odds compared to macrocytosis. NNRTI treatment was associated with higher odds of anaemia compared to INSTI treatment (AOR 5.231, 95% CI 1.04–26.33). Traditional risk factors for anaemia like CD4+ count and tuberculosis infection were not significant.

Conclusion
We found a higher prevalence of anaemia and moderate-to-severe anaemia in virally suppressed PLWH, suggesting factors beyond HIV contribute to the persistence of anaemia in this cohort. Women, lower lymphocyte count, higher BMI, low mean corpuscular volume (microcytosis) indicative of microcytic anaemia, and NNRTI-based ART regimens were independently associated with moderate-to-severe anaemia. Further research is warranted to explain the underlying mechanisms and optimize clinical management to improve outcomes among virally suppressed PLWH.