bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicomponent supervised tele-rehabilitation versus home-based self-rehabilitation management after anterior cruciate ligament reconstruction: a study protocol for a randomized controlled trial
Authors: Wang Kexin , Peng Linbo , You Mingke , Deng Qian , Li Jian
Published: June 2024

Introduction

Our study aims to assess the effectiveness of multicomponent supervised tele-rehabilitation compared to home-based self-rehabilitation management in patients following anterior cruciate ligament reconstruction (ACLR).

Methods

The current study is designed as a single-center, single-blinded, randomized controlled, two-arm trial. Participants will be randomized and allocated at a 1:1 ratio into either a multicomponent supervised tele-rehabilitation group or a home-based self-rehabilitation group. All participants receive uniform preoperative education through the HJT software. Participants in the intervention group undergo multicomponent supervised tele-rehabilitation, while those in the control group follow a home-based self-rehabilitation program. All the participants were assessed and measured for the included outcomes at the outpatient clinic before the procedure, and in 2, 4, 8, 12, and 24 weeks after ACLR by two assessors. The primary outcome was the percentage of patients who achieve a satisfactory active ROM at the 12 weeks following the ACLR. The satisfactory active ROM was also collected at 2, 4, 8, and 24 weeks after ACLR. The secondary outcomes were active and passive range of motion (ROM), pain, muscle strength, and function results.

Registration details

Ethical approval has been obtained from the West China Hospital Ethics Committee (approval number 2023−1929, December 2023). The trial has been registered on ClinicalTrials.gov (registration number NCT06232824, January 2024).
Optimal antiplatelet therapy after revascularization of left subclavian artery during TEVAR
Authors: Shi Mengxiao , Fang Hong , Wu Ying , Li Han , Sheng Chong , Li Shuchun , Zhou Qing
Published: June 2024

Background

Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is required when treating patients with involvement of LSA. The best antiplatelet therapy after LSA reconstruction is presently uncertain.

Methods

This study retrospectively analyzed 245 type B aortic dissection patients who underwent left subclavian artery revascularization during TEVAR. Out of 245 patients, 159 (64.9%) were in the single antiplatelet therapy (SAPT) group, receiving only aspirin, and 86 (35.1%) were in the dual antiplatelet therapy (DAPT) group, receiving aspirin combined with clopidogrel. During the 6-month follow-up, primary endpoints included hemorrhagic events (general bleeding and hemorrhagic strokes), while secondary endpoints comprised ischemic events (left upper limb ischemia, ischemic stroke, and thrombotic events), as well as death and leakage events. Both univariate and multivariate Cox regression analyses were performed on hemorrhagic and ischemic events, with the Kaplan-Meier method used to generate the survival curve.

Results

During the six-month follow-up, the incidence of hemorrhagic events in the DAPT group was higher (8.2% vs. 30.2%, P < 0.001). No significant differences were observed in ischemic events, death, or leakage events among the different antiplatelet treatment schemes. Multivariate Cox regression analysis showed that DAPT (HR: 2.22, 95% CI: 1.07–4.60, P = 0.032) and previous chronic conditions (HR:3.88, 95% CI: 1.24–12.14, P = 0.020) significantly affected the occurrence of hemorrhagic events. Chronic conditions in this study encompassed depression, vitiligo, and cholecystolithiasis. Carotid subclavian bypass (CSB) group (HR:0.29, 95% CI: 0.12–0.68, P = 0.004) and single-branched stent graft (SBSG) group (HR:0.26, 95% CI: 0.13–0.50, P < 0.001) had a lower rate of ischemic events than fenestration TEVAR (F-TEVAR). Survival analysis over 6 months revealed a lower risk of bleeding associated with SAPT during hemorrhagic events (P = 0.043).

Conclusions

In type B aortic dissection patients undergoing LSA blood flow reconstruction after synchronous TEVAR, the bleeding risk significantly decreases with the SAPT regimen, and there is no apparent ischemic compensation within 6 months. Patients with previous chronic conditions have a higher risk of bleeding. The CSB group and SBSG group have less ischemic risk compared to F-TEVAR group.
Ultrasonographic and histopathological investigation of the effect of N-acetylcysteine on doxorubicin-induced ovarian and uterine toxicity in rats
Authors: Üstüner Evren , Yıldırım Ebru , Macun Hasan Ceyhun , Ekici Hüsamettin , Şahin Yaşar , Güncüm Enes , Anteplioğlu Tuğçe , Elifoğlu Taha Burak , Bozkaya Esra
Published: June 2024

Background

This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis.

Methods

Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). The ovaries were examined using B-mode US on days 1, 14, and 21, and the histopathological examinations of the ovaries and the uterus were undertaken after sacrifice on day 22.

Results

Histomorphological analyses showed that ovarian weight decreased after DOX administration in Group B but not in Group E. US revealed a transient increase in ovarian size in Group B and E, reverting to baseline levels over time, as well as a progressive increase in peritoneal fluid in Groups B and E. Group B exhibited a significant decrease in the thickness of the endometrium and myometrium and uterine cornual length, which was not observed in Group E. Histopathological examination showed that DOX caused a decline in follicular count, especially in primordial, secondary, and Graafian follicles, and resulted in follicular atresia, predominantly in Group B. Destructive degeneration/necrosis and vascular changes were most prominently seen in the corpus luteum of Groups C and B. In NAC-treated rats (Groups E and F), although germ cell damage was present, atretic follicles and vascular changes, such as hyperemia and congestion, were reduced. The anti-müllerian hormone (AMH) level was the highest in Group F.

Conclusions

NAC, an antioxidant, attenuated DOX-induced gonadotoxicity in rats.
Evaluating the effectiveness of early urethral catheter removal combined with intermittent catheterization for promoting early recovery of bladder function after laparoscopic radical hysterectomy: a study protocol for a randomized controlled trial
Authors: Chen Yanli , Li Ling , Shi Yuanxiang , Rong Xin , Wang Yan , Wu Jiaojiao , Liang Xiaolong , Wu Zhimin
Published: June 2024

Background

Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction.

Methods

Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study’s primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle.

Discussion

The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery.

Trial registration

ChiCTR2200064041, registered on 24th September, 2022.
African swine fever virus DNA is present in non-biting flies collected from outbreak farms in Romania
Authors: Balmoș Oana Maria , Ionică Angela Monica , Horvath Cintia , Supeanu Alexandru , Moțiu Monica , Ancuceanu Beatris Corina , Tamba Paula , Bărbuceanu Florica , Cotuțiu Vlad , Coroian Mircea , Dhollander Sofie , Mihalca Andrei Daniel
Published: June 2024

Background

African swine fever (ASF) is a highly contagious and severe haemorrhagic disease of Suidae, with mortalities that approach 100 percent. Several studies suggested the potential implication of non-biting dipterans in the spread of ASFV in pig farms due to the identification of the ASFV DNA. However, to our knowledge, no study has evaluated the viral DNA load in non-biting dipterans collected in outbreak farms and no risk factors have been analysed. In this context, our study aimed to analyse the risk factors associated with the presence of non-biting dipterans collected from ASF outbreaks in relation to the presence and load of viral DNA.

Methods

Backyard farms (BF), type A farms (TAF), and commercial farms (CF), were targeted for sampling in 2020. In 2021, no BF were sampled. Each farm was sampled only once. The identification of the collected flies to family, genus, or species level was performed based on morphological characteristics using specific keys and descriptions. Pools were made prior to DNA extraction. All extracted DNA was tested for the presence of the ASFV using a real-time PCR protocol. For this study, we considered every sample with a CT value of 40 as positive. The statistical analysis was performed using Epi Info 7 software (CDC, USA).

Results

All collected non-biting flies belonged to five families: Calliphoridae, Sarcophagidae, Fanniidae, Drosophilidae, and Muscidae. Of the 361 pools, 201 were positive for the presence of ASFV DNA. The obtained CT values of the positive samples ranged from 21.54 to 39.63, with a median value of 33.59 and a mean value of 33.56. Significantly lower CT values (corresponding to higher viral DNA load) were obtained in Sarcophagidae, with a mean value of 32.56; a significantly higher number of positive pools were noticed in August, mean value = 33.12.

Conclusions

Our study brings compelling evidence of the presence of the most common synanthropic flies near domestic pig farms carrying ASFV DNA, highlighting the importance of strengthening the biosecurity measures and protocols for prevention of the insect life cycle and distribution.

Graphical Abstract
Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial
Authors: Obonyo Charles O. , Rawago Fredrick O. , Makworo Nicholas K. , Muok Erick M. O.
Published: June 2024

Background

Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis.

Methods

This was an open-label, randomised clinical trial involving 426 school-aged children (7–15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.

Results

Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.

Conclusions

A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.

Graphical abstract
Diabetes surpasses obesity as a risk factor for low serum testosterone level
Authors: Khalil Samir H. Assaad , Dandona Paresh , Osman Nermin A. , Assaad Ramy Samir , Zaitoon Basma Tayseer Abdalla , Almas Amal Abdulaziz , Amin Noha Gaber
Published: June 2024

Background

Male obesity is one of the most associated factors with substandard testosterone levels. However, there is growing evidence linking low testosterone levels to insulin resistance and diabetic complications. We aimed to study the impact of diabetes mellitus on testosterone levels and to assess the correlation of various clinical and biochemical factors with hypogonadism.

Subjects and methods

This case-control study was conducted on 160 adult males categorized into four equal groups (40 each); Group A: lean men with T2DM, Group B: obese with T2DM, Group C: lean with normal glycemic profile, Group D: obese with normal glycemic profile. Serum total testosterone (TT), SHBG and HbA1c have been measured. Free testosterone (cFT) and HOMA-IR were calculated.

Results

A significant negative correlation of serum TT and cFTwith BMI (r -0.16, p 0.04/ r -0.26, p < 0.001, respectively) and with waist circumference (WC) (r -0.23, p 0.003 and r -0.3, p < 0.001, respectively). A significant decrease in TT and cFT in the diabetes group versus the non-diabetes one (p < 0.001 for both). TT level was significantly lower in the diabetic lean group than in the non-diabetic lean (p < 0.001), and even significantly lower than in the non-diabetic obese (p < 0.001). TT level in the diabetic obese group was lower than in the non-diabetic obese (p < 0.001). The same for cFT level, lower in the diabetic lean group than in non-diabetic lean (p < 0.001) and lower in the diabetic obese than in the non-diabetic obese (p < 0.001). Concomitant significant reduction in SHBG in the diabetes group (p < 0.001). Linear regression analysis revealed that TT significantly correlated with HOMA-IR. HOMA-IR with WC, age and the duration of diabetes correlated significantly with cFT. In our model, HOMA-IR and HbA1c accounted for approximately 51.3% of TT variability (adjusted R-squared 0.513).

Conclusions

The impact of T2DM on serum testosterone levels was more significant than that of obesity. Our study showed a decrease in SHBG together with cFT among the diabetes group. Hypogonadism is significantly correlated to insulin resistance and poor glycemic control, which implies another perspective on the impact of suboptimal glycemic control on the development of hypogonadism.
Limited training and transfer effects in older and young adults who participated in 12 sessions of process-based working memory training. A three-armed pretest-posttest design study
Authors: Zając-Lamparska Ludmiła
Published: June 2024

Objective

Numerous studies confirm the effectiveness of cognitive training in older adults. However, there is limited evidence of the transfer occurrence. The part of the study presented here tested the effect of 12 process-based working memory training sessions on the performance of the trained task (training effect) and other cognitive tasks (transfer effect). A pretest-posttest study design with one experimental group and two control (passive and active) groups. The sample comprised three groups of older adults: experimental (n = 25), passive control (n = 22), active control (n = 7), and young adults: experimental (n = 25), passive control (n = 25), and active control (n = 12). The study was registered after completion with a ClinicalTrials.gov Identifier: NCT06235840 on 31 January 2024.

Results

Under the influence of training, the performance of the trained task improved significantly, but only in young adults. Transfer of WM training effects was not revealed. Among young adults, a testing effect was observed for the indicator of attentional focus and psychomotor speed. Moreover, the obtained results suggest the transfer from practice in multi-domain training, implemented in the active control group, to tasks that require the use of fluid intelligence. However, this finding should be interpreted with great caution due to the small size of active control groups.
The criteria used to rule out mild cognitive impairment impact dementia incidence rates in subjective cognitive decline
Authors: Whitfield Tim , Chouliaras Leonidas , Morrell Rachel , Rubio David , Radford Darren , Marchant Natalie L. , Walker Zuzana
Published: June 2024

Background

The research criteria for subjective cognitive decline (SCD) exclude mild cognitive impairment (MCI), but do not stipulate the use of specific MCI criteria. This study compared different approaches to defining (i.e., excluding) MCI during the ascertainment of SCD, focusing on the impact on dementia incidence rates in SCD.

Methods

This cohort study utilized routine healthcare data collected in the Essex Memory Clinic from 1999 to 2023. Two different operationalizations of the SCD criteria were used to categorize the cohort into two SCD patient samples. One sample was based on local clinical practice – MCI was excluded according to the Winblad criteria (this sample was termed SCDWinblad). The other sample was created via the retrospective application of the Jak/Bondi criteria for the exclusion of MCI (termed SCDJak/Bondi). Only patients aged ≥ 55 years at baseline with ≥ 12 months follow-up were considered for inclusion. The initial clinical/demographic characteristics of the samples were compared. Rates of incident dementia were calculated for each sample, and unadjusted and Mantel-Haenszel-adjusted incidence rate ratios were calculated to compare dementia incidence between the SCD samples.

Results

The Essex Memory Clinic database included 2,233 patients in total. The SCD and study eligibility criteria were used to select SCDWinblad (n = 86) and SCDJak/Bondi (n = 185) samples from the database. Median follow-up (3 years) did not differ between the two samples. The SCDJak/Bondi sample was significantly older than the SCDWinblad at first assessment (median age: 74 versus 70 years) and had poorer scores on tests of global cognition, immediate and delayed verbal recall, and category fluency. Following adjustment for age, the dementia incidence rate ratio [95% confidence interval] was 3.7 [1.5 to 9.3], indicating a significantly greater rate of progression to dementia in SCDJak/Bondi.

Conclusions

This study highlights that the approach used to ascertain SCD has important implications for both SCD phenotypes and prognosis. This underscores the importance of how MCI is operationalized within SCD studies. More broadly, the findings add to a growing body of work indicating that objective cognition should not be overlooked in SCD, and offer a potential explanation for the heterogeneity across the SCD prognostic literature.
Pseudomyxoma peritonei leading to “jelly belly” abdomen: a case report and review of the literature
Authors: Garg Priyanka , Garg Nikhil , Peer Sameer , Chholak Deepika , Kaur Manjit
Published: June 2024

Background

Pseudomyxoma peritonei is an infrequent condition with a global annual incidence of only one to two cases per million people. Mucinous neoplasms, widespread intraperitoneal implants, and mucinous ascites characterize it. Currently, most clinicians misdiagnose this condition, which leads to delayed management.

Case presentation

A 44-year-old North Indian female presented with a 1.5-month history of an abdominal lump. Physical examination revealed a sizeable abdominopelvic mass at 36 weeks. Contrast-enhanced computed tomography showed a massive multiloculated right ovarian cystic mass measuring 28 × 23 × 13 cm with mild ascites and elevated carcinoembryonic antigen levels (113.75 ng/ml). A provisional diagnosis of ovarian mucinous neoplasm was made, for which the patient underwent laparotomy. Intraoperatively, there were gross mucinous ascites, along with a large, circumscribed, ruptured right ovarian tumor filled with gelatinous material. The appendicular lump was also filled with mucinous material along with the omentum, ascending colon, right lateral aspect of the rectum, splenic surface, and small bowel mesentery. Cytoreductive surgery was performed along with an oncosurgeon, including total abdominal hysterectomy with bilateral salpingoophorectomy, omentectomy, right hemicolectomy, lower anterior resection, ileo-transverse stapled anastomosis with proximal ileal loop diversion stoma, excision of multiple peritoneal gelatinous implants, and peritoneal lavage. Histopathology and immunohistochemistry confirmed the presence of intestinal-type mucinous carcinoma. Postoperatively, the patient was given six cycles of chemotherapy. She tolerated it without any specific morbidity and had an uneventful recovery. Postoperative follow-up at 15 months revealed normal tumor marker levels and abdominal computed tomography findings and no signs suggestive of local recurrence or distal metastases.

Conclusions

Pseudomyxoma peritonei is a rare disease that is frequently misdiagnosed in the preoperative phase. Therefore, radiologists and clinicians should maintain a high index of suspicion for accurate diagnosis and multidisciplinary management.
Influence of soil properties on selenium concentration in paddy soil and rice grains in the hilly regions of southern China
Authors: Shang Guiduo , Zhou Weijun , Liu Rui , Zhou Yuzhou , Xu Zhangqian , Cui Haojie , Cai Yixiang
Published: June 2024

Background

Selenium (Se) is essential for human health and is predominantly obtained from dietary sources, particularly rice in Hunan Province, a significant rice-producing region in southern China. Investigating the relationship between Se levels in paddy soil and rice grains, along with the associated influencing factors, is critical for enhancing Se-enriched food security.

Results

Analysis of 128,992 samples collected between 2019 and 2022 revealed that the soil Se concentration in Hunan exceeded the global average, with rice grains showing promising potential for Se enrichment. Various analytical methods, including statistical analyses, co-occurrence networks, and correlation heatmaps, were utilized to scrutinize the extensive dataset. Additionally, partial least squares path analysis elucidated the interactive effects of influencing factors on soil Se concentration, rice grain Se concentration, and Se bioconcentration factor (BCF). Soil parent materials significantly affected soil Se concentration, rice grain Se concentration, and Se BCF (p < 0.01). Factors such as soil cation exchange capacity, soil organic matter, slope, and soil concentrations of Cu, Mn, and Zn demonstrated positive correlations with soil Se concentration. Similarly, these factors exhibited positive associations with rice grain Se concentration. Conversely, negative correlations were observed between certain factors and Se BCF. As a result, predictive models were developed for soil Se, rice grain Se concentration, and Se BCF.

Conclusions

This study contributes valuable insights to inform policy-making for Se-enriched food production and to ensure regional nutritional equilibrium. Caution is recommended in areas with excessive Se levels to prevent potential poisoning risks.
Biological control of Spodoptera frugiperda (Nixon) (Lepidoptera: Noctuidae) in new invaded countries using insect pathogens
Authors: Abbas Mohamed Samir Tawfik
Published: June 2024

Background

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Nixon) (Lepidoptera: Noctuidae), is the major insect pest that infests cereal crops recently in African and Asian countries. The insect is polyphagous that attacks large numbers of host plants, especially maize and rice, causing considerable losses in their annual yield. The integrated pest management (IPM) of the insect depended mainly on insecticides and to some extent on biological control agents including insect pathogens (nematodes, fungi, bacteria and viruses).

Results

Different species of entomopathogens (nematodes, fungi, viruses and bacteria) infecting the insect could be isolated in such newly invaded countries. Laboratory and field experiments indicated that the insect was found to be susceptible to the isolated entomopathogens, and thus, they could be promising biocontrol agents against this insect.

Conclusion

This review article proved the susceptibility of S. frugiperda to the most of tested entomopathogens. However, more field studies have to be carried out in order to include such entomopathogens within integrated pest management programs against this insect pest.
Metataxonomic and metabolomic profiling revealed Pinus koraiensis cone essential oil reduced methane emission through affecting ruminal microbial interactions and host-microbial metabolism
Authors: Choi Y. , Lee S. J. , Kim H. S. , Eom J. S. , Jo S. U. , Guan L. L. , Lee S. S.
Published: June 2024

Background

Pinus koraiensis cone essential oil (PEO) contains functional compounds such as monoterpene hydrocarbons, and the administration of PEO reduced methane (CH4) emissions during growing phase of goats. However, the mode of action of PEO driven CH4 reduction is not known, especially how the administration of PEO can affect rumen microbiota and host metabolism in goats during the fattening phase. This study aimed to elucidate the potential microbial and host responses PEO supplementation in goats using metataxonomics (prokaryotes and protozoa) and metabolomics (rumen fluid and serum).

Results

Ten fattening Korean native goats were divided into two dietary groups: control (CON; basal diet without additives) and PEO (basal diet + 1.5 g/d of PEO) with a 2 × 2 crossover design and the treatment lasted for 11 weeks. Administration of PEO reduced CH4 concentrations in the exhaled gas from eructation by 12.0–13.6% (P < 0.05). Although the microbial composition of prokaryotes (bacteria and archaea) and protozoa in the rumen was not altered after PEO administration. MaAsLin2 analysis revealed that the abundance of Selenomonas, Christensenellaceae R-7 group, and Anaerovibrio were enriched in the rumen of PEO supplemented goats (Q < 0.1). Co-occurrence network analysis revealed that Lachnospiraceae AC2044 group and Anaerovibrio were the keystone taxa in the CON and PEO groups, respectively. Methane metabolism (P < 0.05) was enriched in the CON group, whereas metabolism of sulfur (P < 0.001) and propionate (P < 0.1) were enriched in the PEO group based on microbial predicted functions. After PEO administration, the abundance of 11 rumen and 4 serum metabolites increased, whereas that of 25 rumen and 14 serum metabolites decreased (P < 0.1). Random forest analysis identified eight ruminal metabolites that were altered after PEO administration, among which four were associated with propionate production, with predictive accuracy ranging from 0.75 to 0.88. Additionally, we found that serum sarcosine (serum metabolite) was positively correlated with CH4 emission parameters and abundance of Methanobrevibacter in the rumen (|r|≥ 0.5, P < 0.05).

Conclusions

This study revealed that PEO administration reduced CH4 emission from of fattening goats with altered microbial interactions and metabolites in the rumen and host. Importantly, PEO administration affected utilizes various mechanisms such as formate, sulfur, methylated amines metabolism, and propionate production, collectively leading to CH4 reduction. The knowledge is important for future management strategies to maintain animal production and health while mitigate CH4 emission.
Multi-model approach for optimizing cold-wave resilient maize selection: unveiling genotype-by-environment interaction and predicting yield stability
Authors: Kunwar Chitra Bahadur , Basnet Bikas , Sunuwar Samjhana , Mahato Deep Narayan , Chaudhari Ramdas , Upadhya Jharna , Pokhrel Pragya
Published: June 2024

Cold waves both significantly reduce yield & damage crops as well; unforeseeable nature of cold waves makes it challenging for farmers to manage risk. Thus, we aim to select maize hybrids that thrive under cold stress (both escaping early cold-waves and tolerating cold snaps); pinpoint stable, high-yielding hybrids ideal for regions prone to cold stress. In this investigation 2 years winter trial in Nepal was appraised on diverse maize hybrids for cold wave tolerant, stable across four stations with a Randomized Complete Block Design & 3 replications at each station. Likewise, this research employed 4 statistical methods both fixed effect and linear mixed model: genotype-environment interactions (AMMI), visually analyzes genotype performance and stability across environments (GGE) breeding values of genotypes for selection (BLUP), multiple traits for selection (MTSI). This scholarship revealed significant (P < 0.001) impacts of genotype, environment, and their interaction (GEI) on yield. This GEI, accounting for 100% of yield variance, was mainly captured by 3 principal components, with the first explaining 49%. Notably, mixed-effects models and biplots identified superior hybrids exhibiting both high average yields and consistent performance. GGE biplot analysis unveiled high-yielding and adaptable: GK3157, NK6607, RMH1899 Super, GK3254, RMH666, Shan 111, DKC9149, and Sweety-1. Further, BLUP and WAASBYY analyses delineated the superior performers and stabilized hybrids for yield, with DKC9141, Uttam 121, NK6607, MM2929, RMH-666, GK 3254, and GK3157, and RMH-1899 super candidates for both high yield and stability. In Nepalgunj, Delta 3333, MM2122, and Shaan 111 excelled in both yield and stability, while Rampur favored Rampur Hybrid 6 and MM2424 for stability. Parwanipur and Tarahara shared similar winners for stability and yield, including MM2122, Shaan 111, and Delta 3333 in Parwanipur, and NK7884, MM2424, and Delta 2222 in Tarahara. Based on Multi genotype ideotype distance (MGDI), 9 hybrids were selected for yield and stability, including MM 2033, NK 6607, Sweety 1 so on; exhibited escape to cold waves whilst GK3254, TMMH-846, and MM-9442, were chosen for cold waves adapted hybrids. Moreover, by identifying cold-tolerant maize hybrids, this study has potential to mitigate risks for farmers (economic burden, crop failure) and bolster food security.
Nucleated red blood cells as a prognostic marker for mortality in patients with SARS-CoV-2-induced ARDS: an observational study
Authors: Kirsch Anna , Niebhagen Felix , Goldammer Miriam , Waske Sandra , Heubner Lars , Petrick Paul , Güldner Andreas , Koch Thea , Spieth Peter , Menk Mario
Published: June 2024

Background

The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients.

Methods

Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated.

A cut-off level based on the patient’s maximum NRBC value during ICU stay was calculated and further specified according to Youden’s method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed.

Results

413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001).

A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95–7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7–43.3] vs. 21 days [95% CI 18.2–23.8], log-rank test, p < 0.05).

Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2–8.5).

Conclusions

NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making.
Landscape analysis and oncologic outcomes in advanced urothelial carcinoma (UC) by NECTIN4 RNA expression.
Authors: Stewart Tyler F. , Fenton Sarah Elizabeth , Nazari Shayan , Elliott Andrew , Garje Rohan , Salmasi Amirali , Bagrodia Aditya , Nabhan Chadi , VanderWeele David James , McKay Rana R.
Published: June 2024

4585

Background: Advanced UC is a devastating disease, however recent advances with antibody drug conjugates (ADCs), including enfortumab vedotin (EV), have improved outcomes significantly. Currently no biomarkers are clinically available to predict response to therapy. We hypothesized that benefit from EV may correlate with mRNA expression of NECTIN4, the gene encoding the relevant cell surface antigen for EV. Therefore, we performed a landscape analysis of NECTIN4 in advanced UC and correlated expression with oncologic outcomes. Methods: Bladder and upper tract UC samples were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (592 genes or whole exome) and NovaSeq on RNA (whole transcriptome). UC samples were stratified by NECTIN4 mRNA levels into four quartiles. Tumor mutational burden (TMB) totaled somatic nonsynonymous mutations per tumor (high >10 mut/Mb). Insurance claims data were used to calculate survival outcomes using Kaplan-Meier estimates. Overall survival (OS) was calculated from the date of sample collection and date of treatment initiation to date of last follow up. Time on treatment (TOT) was calculated from date of treatment initiation to date of last treatment.Survival analysis was performed between top and bottom quartiles of NECTIN4 expression. Results: A total of 6,395 patient samples were analyzed [n=4335 from primary tumor (3496 bladder/urethra, 839 upper tract), n= 2060 from metastases]. Expression of NECTIN4 was associated with higher rates of mutations in FGFR3 (18.9% vs 6.9%), ERBB2 (11.8% vs 5.9%), pTERT (77.3% vs 62.6%), CCNE1 (5.6% vs 1.7%), SDHC (8.3% vs 0.6%) and with TMB-H status (46.2% vs 35.8%) but lower rates of TP53 mutations (54.6% vs 67.7%). NECTIN4 expression positively correlated with expression of TACSTD2 (TROP2), ERBB2 (HER2) and SLITRK6. Interestingly, NECTIN4 expression inversely correlated with PDL1 expression by IHC (22c3, 26.9% vs 59.2%). Similar findings were found when analysis was performed by primary bladder versus primary upper tract, as well as primary versus metastatic site. NECTIN4 expression was associated with longer OS in the overall population, and improvement in TOT (HR 0.53) and OS (HR 0.67) for patients treated with EV (Table). NECTIN4 expression was not associated with benefit with anti-PD1/L1 therapy. Conclusions: In the largest study investigating NECTIN4 expression in UC, we demonstrate co-expression of TACSTD2 (TROP2), ERBB2 (HER2) and SLITRK6 with NECTIN4. Expression of NECTIN4 correlated with favorable prognosis and predicted benefit from EV. NECTIN4 RNA expression could be a potential biomarker for selecting patients for treatment with EV. Further validation is required. [Table: see text]
Single agent axitinib in the management of patients with progressive pheochromocytoma and paraganglioma.
Authors: Fojo Antonio Tito , Apolo Andrea B , Edgerly Maureen , Pacak Karel , Figg William Douglas , Bates Susan Elaine , Del Rivero Jaydira
Published: June 2024

4602

Background: Malignant pheochromocytomas and paragangliomas remain diseases that present those caring for patients with these diseases the dual challenges of hormonal excess and malignant behavior. Radiolabeled therapy with meta-iodobenzguanine (MIBG) and chemotherapy with a combination of cyclophosphamide, vincristine and dacarbazine can help in the management of patients whose disease has metastasized, but additional options are needed. The phase II FIRSTMAPPP study provided support for use of the tyrosine kinase inhibitor, sunitinib, in these malignancies with median PFS values of 8.9 vs. 3.6 months and ORRs of 31% vs. 8% for sunitinib vs placebo.Median duration of sunitinib therapy was 11 months. Concurrent with this study we launched a single arm trial to examine the activity of a similar TKI, axitinib. We report here the results of that study. Methods: Axitinib was self-administered at a dose of 5 mg every 12 hours continuously in a 28-day cycle. All patients were evaluated for dose adjustments to levels of 2, 3, 7, and 10 mg bid as options with intervals of at least 4 weeks between any dose escalations. Efficacy evaluations using conventional imaging were performed every 12 weeks. Documented evidence of disease progression was required prior to study entry. Results: Nineteen patients were enrolled; two did not receive treatment or less than one week of treatment. A partial response was achieved in 35.3% of patients, with a median reduction of tumor measurements of 34% and a median duration of response of 7.4 months. Median PFS was 7.9 months. Median duration of treatment was 9.5 months. Median OS was 29 months. Axitinib was well-tolerated with treatment-emergent adverse events with an attribution of possible, probable, and definite similar to those previously reported for the agent, including G1/2 fatigue, diarrhea, mucositis, and PPE in 42% to 63% and G1/2/3 hypertension in 79%, all managed with adjustments in antihypertensive medications No patient discontinued axitinib for an adverse event, nor had a prolonged suspension of treatment. Unfortunately, the study has been prematurely terminated by the sponsor. Conclusions: These results together with similar results reported recently with sunitinib provide strong evidence for the efficacy of sunitinib and axitinib, two VEGF tyrosine kinase inhibitors with similar characteristics, in the management of malignant pheochromocytoma and paragangliomas. Axitinib should be started at a dose of 5 mg bid and adjusted as tolerated. Despite its use in individuals with often difficult to treat hypertension, blood pressure management did not present a difficult challenge. Clinical trial information: NCT03839498 .
Comparing treatment modalities for T2N0M0 muscle invasive bladder cancer: A propensity score analysis with the National Cancer Database.
Authors: Pieretti Alberto , Mohanna Mohamed , Sabbagh Saad , Muruve Nicolas , Liang Hong , Fleming Christopher , Weight Christopher , Almassi Nima , Haber Georges-Pascal , Kamat Ashish M. , Arteta-Bulos Rafael , Dinney Colin P.N.
Published: June 2024

4604

Background: Muscle-invasive Bladder Cancer (MIBC) constitutes 25% of bladder malignancies. Per NCCN guidelines, the primary treatment for stage II (T2N0M0) MIBC is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), RC alone, or bladder preservation chemoradiotherapy (BPCRT). This study aims to compare the overall survival between different treatment modalities with an emphasis on patients considered to be best candidates for BPCRT (No hydronephrosis, extensive or multifocal carcinoma in situ (CIS), and tumor size <6cm, ”low-risk”) versus those who are not (“high-risk”). Methods: We queried 12510 patients from the National Cancer Database from 2004-2020 for stage II T2N0M0 MIBC. Patients were divided in low-risk (< 6 cm and no evidence of CIS) or high-risk MIBC. The propensity score matched (PSM) sample was constructed greedy nearest neighbor matching on the logit of the propensity score using a caliper of width equal to 0.2 of the standard deviation of the logit of the propensity score. We used standardized differences (SD) to evaluate how well the covariates were balanced and a value of < 0.1 was considered negligible. The Cox proportional hazards model was performed to compare the survivorships between the PSM paired samples. All data analyses were conducted using SAS version 9.4. Results: Following PSM and risk factor stratification, we found that median overall survival (OS) was lower with BPRCT compared to RC alone or NAC+RC in both risk groups. In the low-risk group, the median OS of BPRCT compared to NAC+RC was 34 and 76 months, respectively (HR = 1.81, 95%CI = (1.25-2.62), p=0.0017 and there was no statistical significant difference in RC compared to NAC+RC median OS (p=0.3459). In the high-risk group, the median OS of BPRCT compared to NAC+RC was 22 and 68 months, respectively (HR = 2.19, 95%CI = (1.86-2.59), p<0.0001) (Table) and the median OS of RC compared to NAC+RC was 79 and 99 months respectively (HR=1.2, 95%CI = (1.11-1.3), p<0.001 (Table). Conclusions: This nationwide study showed that RC was the optimal treatment for low-risk stage 2 MIBC, with improved OS compared with BPCRT and equivalent OR with NAC+RC, without the added cost or morbidity. For high-risk patients NAC+RC was associated with a significant improvement of OS compared to BPCRT and RC alone.[Table: see text]
Association of elevated pulmonary artery systolic pressure with hematologic progression in myeloproliferative neoplasms.
Authors: Leiva Orly , Soo Steven , How Chi-Joan , Smilowitz Nathaniel , Shah Binita , Reynolds Harmony , Hobbs Gabriela , Bernard Samuel
Published: June 2024

6575

Background: Pulmonary hypertension (PH) is associated with myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Prior studies have suggested that patients with MPN and cardiovascular disease (CVD) with PH are at increased risk of progression of MPN to secondary MF or acute leukemia. Further characterization of risk of hematologic progression among all-comers with MPN is lacking. Methods: In this single-center, retrospective cohort study, patients with MPN and ≥ 1 transthoracic echocardiogram (TTE) after diagnosis were identified. PH was defined as an estimated pulmonary artery systolic pressure (PASP) ≥ 40 mmHg on first TTE after MPN diagnosis. Primary outcome was hematologic end-point, composite of progression of MPN to secondary MF, acute leukemia, death related to MPN, or bone marrow transplantation (BMT). Secondary endpoint was major adverse cardiovascular events (MACE), composite of arterial thrombosis, venous thromboembolism, heart failure (HF) and CV death. Multivariable Fine-Gray competing-risk regression (with non-hematologic death and non-CV death as competing-risks for hematologic endpoint and MACE, respectively) were used to estimate risk of outcomes. Results: Of 272 patients with MPN identified, 69 (25.4%) had PH on first TTE. Patients with PH were older at MPN diagnosis, had more MF (27.5% vs 11.8%, p = 0.004), and prior HF (18.8% vs 6.4%, p = 0.004). Patients with PH had higher rates of secondary mutations (24.6% vs 13.3%, p = 0.024), particularly in ASXL1 (8.7% vs 2.5%, p = 0.034) and RUNX1(4.3% vs 0, p = 0.016). After a median follow-up of 46.2 months (IQR 29.3, 69.1), hematologic endpoint (30.4% vs 8.4%, p < 0.001 and MACE (53.6% vs 23.6%, p < 0.001) were higher in PH group. Rates of secondary MF (13.0% vs 4.9%, p = 0.030), acute leukemia (13.0% vs 0.5%, p < 0.001), and death related to MPN (8.7% vs 1.5%, p = 0.01) but not BMT (2.9% vs 3.4%, p = 1.00) were higher in PH. After adjusting for age, sex, MPN type, mutation, and time from MPN to first TTE, PH was associated with higher risk of hematologic endpoint (aSHR 3.70, 95% CI 1.55 – 8.82). After adjusting for the same variables as well as LVEF, left atrial size, prior CVD, PH was associated with increased risk of MACE (aSHR 2.38, 95% CI 1.42 – 3.97). Conclusions: Among patients with MPN, PH on TTE was associated with increased risk of hematologic progression and MACE. Prospective studies are needed to confirm our findings. Further investigation into the underlying mechanisms of PH in MPN should be conducted. [Table: see text]