bluuebunny/crossref_metadata_2025 huggingface dataset:
Multipotent fetal stem cells in reproductive biology research
Authors: Rosner Margit , Horer Stefanie , Feichtinger Michael , Hengstschläger Markus
Published: June 2023

Due to the limited accessibility of the in vivo situation, the scarcity of the human tissue, legal constraints, and ethical considerations, the underlying molecular mechanisms of disorders, such as preeclampsia, the pathological consequences of fetomaternal microchimerism, or infertility, are still not fully understood. And although substantial progress has already been made, the therapeutic strategies for reproductive system diseases are still facing limitations. In the recent years, it became more and more evident that stem cells are powerful tools for basic research in human reproduction and stem cell-based approaches moved into the center of endeavors to establish new clinical concepts. Multipotent fetal stem cells derived from the amniotic fluid, amniotic membrane, chorion leave, Wharton´s jelly, or placenta came to the fore because they are easy to acquire, are not associated with ethical concerns or covered by strict legal restrictions, and can be banked for autologous utilization later in life. Compared to adult stem cells, they exhibit a significantly higher differentiation potential and are much easier to propagate in vitro. Compared to pluripotent stem cells, they harbor less mutations, are not tumorigenic, and exhibit low immunogenicity. Studies on multipotent fetal stem cells can be invaluable to gain knowledge on the development of dysfunctional fetal cell types, to characterize the fetal stem cells migrating into the body of a pregnant woman in the context of fetomaternal microchimerism, and to obtain a more comprehensive picture of germ cell development in the course of in vitro differentiation experiments. The in vivo transplantation of fetal stem cells or their paracrine factors can mediate therapeutic effects in preeclampsia and can restore reproductive organ functions. Together with the use of fetal stem cell-derived gametes, such strategies could once help individuals, who do not develop functional gametes, to conceive genetically related children. Although there is still a long way to go, these developments regarding the usage of multipotent fetal stem cells in the clinic should continuously be accompanied by a wide and detailed ethical discussion.
User needs over time: the market and technology maturity model (MTMM)
Authors: Silberer Jan , Astfalk Stefanie , Planing Patrick , Müller Patrick
Published: June 2023

This paper conceptualizes how consumers perceive innovations at different stages of technology maturity. The market and technology maturity model (MTMM) combines the constructs of acceptability, acceptance, and adoption with the widely used technology readiness level (TRL). The MTMM proposes that different aspects impact users’ attitudes and behavior at different stages of technology maturity. To demonstrate the effect of technology maturity on the acceptance factors, a review was conducted based on previous studies on the acceptance of new technologies at various stages of technological maturity. The findings demonstrate that performance expectancy remains stable across the TRL stages, but effort expectancy tends to gain importance only after TRL 7. This indicates that consumers do not consider effort when the technology is still in early development. The results show that the importance of technology acceptance constructs differs across the stages of technology maturity. A limitation of this study is that only the most commonly used factors influencing acceptance have been considered. Future meta-studies should confirm the hypothesis with other factors such as social influence and hedonic motivation.
Multifamily therapy for adolescent eating disorders: a study of the change in eating disorder symptoms from start of treatment to follow-up
Authors: Funderud Ingrid , Halvorsen Inger , Kvakland Anne-Lise , Nilsen Jan-Vegard , Skjønhaug Jeanette , Stedal Kristin , Rø Øyvind
Published: June 2023

Background

This study aimed to evaluate multifamily therapy (MFT) for adolescents with eating disorders (EDs) in a clinical setting, by presenting the outcome of families participating in this treatment at a specialist ED service. MFT was an adjunct to treatment at local mental health services. In particular, the study aimed to present the change in eating disorder symptoms and psychological distress from before to after treatment and at a 6 months follow-up.

Methods

Participants were 207 adolescents receiving outpatient MFT (10 or 5 months) at Oslo University Hospital in Norway between 2009 and 2022. Adolescents had heterogeneous ED presentations, with a preponderance of anorexia nervosa (AN) and atypical AN. All participants completed pre- and post-treatment questionnaires [The eating disorder examination questionnaire (EDE-Q) and the strengths and difficulties questionnaire (SDQ)]. 142 adolescents additionally completed the same questionnaires at 6 months follow-up. Weight and height were measured at all time points.

Results

Linear mixed model analyses showed that from start of treatment to follow-up, there was a significant increase in BMI percentile (p < 0.001) and a significant decrease in EDE-Q global score (p < 0.001) and SDQ total score (p < 0.001).

Conclusions

The study shows that adolescents with an eating disorder who received adjunct outpatient MFT in a real world clinical setting, experienced reductions in ED symptoms comparable to that found in a randomized controlled trial.

Trial registration: The data used in this study was collected as part of routine clinical procedures for quality assurance and trial registration is therefore not required.
Antifungal and consolidation properties of linen textiles treated with silver nanoparticles loaded on hydroxypropyl cellulose polymer
Authors: Abo-Elmaaref Mahmoud , Marouf Mohamed , Mohamed W. S. , Abdel Wahab Walaa A.
Published: June 2023

Microorganisms are considered one of the most dangerous deterioration factors to cellulosic textiles, especially textiles made of linen fibers. Many of the traditional methods of resistance to microorganisms that infect textiles were used in the past, but they were of low effectiveness and high toxicity for those who applied these methods. The study used silver nanoparticles (AgNPs) prepared by the chemical reduction of silver nitrate (AgNO3) in the presence of a polyvinylpyrrolidone (PVP) polymer as a stabilizing agent in inhibiting fungal strains Aspergillus flavus, Trichoderma sp. and Penicillium duclauxii that were isolated from the ancient linen piece No. 1345 preserved in the Sohag National Museum. The properties of the silver nanoparticles prepared and loaded on hydroxypropyl cellulose (Klucel G 1%) polymer were studied by many of examination and analysis methods such as TEM, XRD and FTIR. Evaluating the effectiveness of AgNPs/Klucel G by using well-cut diffusion technique revealed that the best concentration of AgNPs in inhibiting fungal strains is 3%. The results of treating raw and dyed linen textiles using AgNPs/Klucel G also indicated an improvement in the mechanical and chemical properties of the treated textiles. One of the most important results of the study is obtaining raw and dyed linen textiles with resistant properties to isolated fungal strains up to 3 months of treatment.

Graphical Abstract
Operational strategies to alleviate thermal impacts of the large-scale borehole heat exchanger array in Beijing Daxing Airport
Authors: Ren Yaqian , Kong Yanlong , Huang Yonghui , Bie Shu , Pang Zhonghe , He Jichao , Yi Wei , He Bin , Wang Jiyang
Published: June 2023

Large-scale ground source heat pump (GSHP) systems are increasingly used for space heating and cooling. In comparison with smaller ones, large GSHP systems are often coupled with much more borehole heat exchangers (BHEs). Because of the intense thermal interactions between BHEs, they are more susceptible to significant ground temperature changes. Meanwhile, they possess the advantage that their operational strategies can be applied with a high degree of freedom, which presents chances to alleviate intense thermal interactions. In this study, we used a new performance indicator to access the effectiveness of GSHP operational strategies on alleviating thermal anomalies. The Daxing Airport GSHP system, contains 10,497 BHEs and is the largest in the world; therefore, it was selected as the test case for performance enhancement through operational strategies. We established a 2D model to predict ground temperature changes during the 50-year operation of the BHEs. First, it was revealed that the most severe thermal anomalies in the study area mainly occurred both within and between the BHE arrays, which should be mitigated. To alleviate the thermal anomalies caused by the thermal interactions of BHEs, operational strategies were applied by adjusting the cooling/heating starting sequence, setting time-dependent thermal loads, and reallocating thermal loads according to the position of the BHEs. Our study demonstrates that only the operation strategy that adjusts the cooling/heating starting sequence is beneficial for different BHE layouts, while the operational strategy that reallocates the thermal loads depending on BHEs position may be only effective for specific BHE layouts. In addition, our new performance indicator can be used to evaluate the effectiveness of the operational strategies and determine the spacing of adjacent BHE arrays. Therefore, it benefits the operation management of BHE array and design of BHE layout, and further guarantees the sustainable operation of the GSHP system.
Successful treatment of postoperative nonobstructive recurrent cholangitis by tract conversion surgery after total pancreatectomy: a case report
Authors: Odaira Masanori , Toriumi Fumiki , Hoshino Shota , Iwama Nozomi , Ito Yasuhiro , Endo Takashi , Harada Hirohisa
Published: June 2023

Background

Postoperative cholangitis is a complication of biliary reconstruction during hepatobiliary pancreatic surgery. Most cases are associated with anastomotic stenosis, but there are also cases of cholangitis without stenosis, and treatment can be difficult, especially in patients with recurrent symptoms. In this report, we describe a case of repeated nonobstructive cholangitis in a patient after total pancreatectomy, in which a good outcome was obtained after performing tract conversion surgery.

Case presentation

The patient was a 75-year-old man. He underwent total pancreatectomy for stage IIA cancer of the pancreatic body, hepaticojejunostomy via the posterior colonic route, gastrojejunostomy and Braun anastomosis via the anterior colonic route using the Billroth II method. The patient had a good postoperative course and was receiving adjuvant chemotherapy on an outpatient basis, but he developed his first episode of cholangitis 4 months after surgery. Although conservative treatment with antimicrobial agents was successful, the patient continued to have recurrent biliary cholangitis and was repeatedly admitted and discharged from the hospital. Since stenosis at the anastomosis was suspected, endoscopic observation of the anastomosis was performed using small bowel endoscopy for close examination, but no apparent stenosis was observed. Small bowel imaging indicated a possible influx of contrast medium into the bile duct, and reflux due to food residue was suspected as the cause of cholangitis. Since conservative treatment alone did not suppress the flare-up of symptoms, the decision was made to perform tract conversion surgery for curative purposes. The afferent loop was cut midstream, and jejunojejunostomy was performed downstream. The postoperative course was good, and the patient was discharged on the 10th day after surgery. He is currently an outpatient and has been free of cholangitis symptoms for 4 years without cancer recurrence.

Conclusions

Although the diagnosis of nonobstructive retrograde cholangitis can be difficult, surgical treatment should be considered in patients with recurrent symptoms and refractory treatment.
Chemo-preventive effects and antitumorigenic mechanisms of beer and nonalcoholic beer toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) - induced lung tumorigenesis in A/J mice
Authors: Takata Jun , Kiura Katsuyuki , Nakasuka Takamasa , Hirabae Atsuko , Arimoto-Kobayashi Sakae
Published: June 2023

We investigated the chemopreventive effects of beer, nonalcoholic beers (NABs), and beer-components (glycine betaine (GB)) on NNK-induced lung tumorigenesis in A/J mice, and the possible mechanisms underlying the antitumorigenic effects of beer, NABs, and beer-components. Beer, NABs, and GB reduced NNK-induced lung tumorigenesis. We investigated the antimutagenicity of beer, NABs and beer-components (GB and pseudouridine (PU)) toward the mutagenicity of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Beer, NABs, and beer components were antimutagenic toward MNNG and NNK in the Ames test using S. typhimurium TA1535. In contrast, MNNG and NNK mutagenicity detected in S. typhimurium YG7108, a strain lacking O6-methylguanine DNA methyltransferases (ogtST and adaST) did not decrease in the presence of beer, NABs, or beer components, suggesting that they may mediate its antimutagenic effect by enhancing DNA damage repair. Phosphorylation of Akt and STAT3, with or without epidermal growth factor stimulation, in lung epithelial-like A549 cells were significantly decreased following beer, NABs, GB and PU. They targeted both the initiation and growth/progression steps of carcinogenesis, specifically via antimutagenesis, stimulation of alkyl DNA-adduct repair, and suppression of Akt- and STAT3- mediated growth signaling. GB and PU may contribute, in part, to the biological effects of beer and NABs via the suppression of Akt and STAT3 phosphorylation.
Factors affecting in vitro tuberization of potato
Authors: Mohamed Adel El-Sawy , Girgis Nancy Danial
Published: June 2023

Background

Potato (Solanum tuberosum L.) is one of the most economically important annual vegetable crops. Microtubers can be produced, stored around year and directly transported to market without transferring to fresh media and without acclimatization. Thus reducing the field cycle to obtain sufficient number of seed potatoes and a high level of healthy materials. The aim of this study was to investigate effects of different combinations and concentrations of growth regulators i.e., kinetin (2.5 mg/l) and coumarin (20, 40 and 60 mg/l) alone or in addition to varied concentrations of sucrose (30, 60 and 90 g/l) on in vitro tuberization of potato (Solanum tuberosum) cv. Diamount.

Results

The plantlets were propagated using single-node cuttings cultured on Murashige and Skoog medium containing 0.04 mg/l kinetin and 1.0 mg/l IAA. Shoots (6–7 nodes) from the previous step were cultured into medium supplemented with a factorial combination of sucrose concentrations (30, 60 and 90 g/l), coumarin concentrations (0, 20, 40, and 60 mg/l) and two concentrations of kinetin (0 and 2.5 mg/l). Our results showed that kinetin – induced medium have slightly effect to improve tuberization in vitro. But when kinetin was combined with sucrose, this effect was better when raised sucrose concentration from 30 or 60 to 90 g/l. The highest percentage of tuberization after 8 weeks, highest number of microtuber were obtained with high concentration of sucrose (90 g/l) together with dark condition, at 18–20 °C. Also, the highest concentration of sucrose significantly increased the fresh weight of microtuber. In case of coumarin, results revealed that it has important effect on tuber initiation especially with concentrations 20 mg/l and 40 mg/l; otherwise, the initiation period was minimized after adding kinetin. So, the plantlets must be continuously incubated in coumarin –induce medium plus kinetin for 8 weeks to affect the tuberization response. Also, all the other characters of tuberization process on coumarin-inducing medium could be improved by increasing sucrose concentration to 9 g/l.

Conclusions

Generally, results pointed out that the treatment which consists of kinetin (2.5 mg/l) plus 90 g/l sucrose and 20 mg/l coumarin has the best characteristics of in vitro micro-tuberization.
Risk factors affecting outcome of rhino-orbital-cerebral mucormycosis in COVID-19 patients
Authors: Saleeb Mina Fayez , Sabry Sabry Magdy , Mahmoud Mohammad Salah , Nassif Mena Maher
Published: June 2023

Background

Mucormycosis is a serious life-threatening fungal infection that recently made severe sudden and devastating surge during the second wave of the COVID-19 epidemic with a mortality rate of up to 50%.

Although the causality link between COVID-19 and rhino-orbito-cerebral mucormycosis (ROCM) remains unclear, many factors including poor diabetes control, high doses of steroids, viral-induced lymphopenia, and cytokine storm have been attributed to ROCM in patients with COVID-19.

Orienting to risk factors and early recognition of this potentially fatal opportunistic infection is the key to optimal management and improved outcomes. In these contexts, we conducted a prospective study for 33 patients admitted to our tertiary hospital to determine the risk factors for ROCM in patients with COVID-19 and the cumulative mortality rates.

Results

This study found a statistically significant relation between the fate of death in COVID-MUCOR patients who had presented fever, ophthalmoplegia, facial skin necrosis, and visual loss with those who received dose of steroid to control their respiratory symptoms P < 0.001.

Death from COVID-MUCOR was statistically significant related to the prolonged interval from the onset of the symptoms to start of treatment and intervention. Also, it was found that there was a significant decrease in duration between COVID-19 infection and the start of mucormycosis (days) with incidence of DKA on admission. Nineteen (57.6%) of the patients had uncontrolled diabetes mellitus (hemoglobin A1C (HbA1c) of > 7.0%).

Conclusion

Mucormycosis epidemic was precipitated by a unique confluence of risk factors: diabetes mellitus, widespread use of steroids, and perhaps SARS-CoV-2 infection itself. Restricting steroid use in patients with severe COVID-19 requiring oxygen therapy, and screening for and optimally controlling hyperglycemia, can prevent COVID-MUCOR in a large majority.
SARS-CoV-2 and risk of psychiatric hospital admission and use of psychopharmaceuticals: A nationwide registry study of 4,585,083 adult Danish citizens
Authors: Rømer Valdemar , Sivapalan Pradeesh , Eklöf Josefin , Nielsen Susanne D. , Harboe Zitta B. , Biering-Sørensen Tor , Itenov Theis , Jensen Jens-Ulrik S.
Published: June 2023

Background

Current evidence on the risk of admission- or medication-requiring psychiatric sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited to selected populations, short durations, and loss to follow-up. This study examined if SARS-CoV-2 infection was associated with increased long-term risk of psychiatric admissions and de novo prescription of psychoactive medication in the general population of Denmark.

Methods

Adults (≥18 years) were assigned to either the control or SARS-CoV-2 group based on polymerase chain reaction (PCR) tests between 1 January 2020 and 27 November 2021. Infected subjects were matched 1:5 to control subjects by propensity score. Incidence rate ratios (IRRs) were calculated. Adjusted Cox regression was applied to the unmatched population with SARS-CoV-2 infection as a time-dependent covariate. Follow-up time was 12 months or until the end of the study.

Results

A total of 4,585,083 adults were included in the study. Approximately 342,084 had a PCR-confirmed SARS-CoV-2 infection and were matched 1:5 with 1,697,680 controls. The IRR for psychiatric admission was 0.79 in the matched population (95% confidence interval [CI]: 0.73–0.85, p < 0.001). In the unmatched population, the adjusted hazard ratios (aHR) for psychiatric admission were either below 1.00 or with a 95% CI lower limit of 1.01. SARS-CoV-2 infection was associated with an increased risk of de novo prescription of psychoactive medication in both the matched (IRR 1.06, 95% CI: 1.02–1.11, p < 0.01) and unmatched population (HR 1.31, 95% CI: 1.28–1.34, p < 0.001).

Conclusions

We found a signal of increased use of psychoactive medication, specifically benzodiazepines, among SARS-CoV-2-positive persons, but the risk of psychiatric admissions did not increase.
Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results.
Authors: Meric-Bernstam Funda , Makker Vicky , Oaknin Ana , Oh Do-Youn , Banerjee Susana N. , Gonzalez Martin Antonio , Jung Kyung Hae , Lugowska Iwona A. , Manso Luis , Manzano Aránzazu , Melichar Bohuslav , Siena Salvatore , Stroyakovskiy Daniil , Anoka Chiedozie , Ma Yan , Puvvada Soham D. , Lee Jung-Yun
Published: June 2023

LBA3000

Background: T-DXd is an antibody drug conjugate targeting HER2 and is approved in HER2-expressing breast (BC) and gastric (GC) cancers. HER2 expression is prevalent in other solid tumors. The efficacy of current treatments (Tx) in these populations, including studies with HER2-directed Tx, is modest, revealing a significant unmet medical need. Clinically meaningful activity of T-DXd was seen in HER2-expressing tumors in a phase 1 study (NCT02564900). Methods: DP-02 (NCT04482309) is an open-label phase 2 study of T-DXd 5.4 mg/kg q3w in pts with HER2-expressing (immunohistochemistry [IHC] 3+ or IHC 2+ by local or central testing) locally advanced or metastatic disease that progressed after ≥1 systemic Tx or that has no Tx options. Cohorts with biliary tract (BTC), bladder (URO), cervical (CC), endometrial (EC), ovarian (OC), pancreatic (PC), or other tumors (excluding BC, GC, colorectal cancer, and non-small cell lung cancer) were enrolled. Efficacy and safety were analyzed in all pts who received ≥1 dose of T-DXd. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR), disease control rate, progression-free and overall survival, and safety. Results: At data cutoff (16 Nov 2022; median follow-up, 9.7 mo), 267 pts had been treated (median, 2 prior lines of Tx [range, 0-13]); 75 pts were IHC 3+ and 125 were IHC 2+ by central testing. In all 267 pts, the ORR was 37.1% and median DOR (mDOR) was 11.8 mo; in pts with IHC 3+ expression, the ORR was 61.3% and mDOR was 22.1 mo. ORR per cohort is shown in all pts and those with centrally confirmed HER2 IHC 3+ or IHC 2+ expression. Grade (G) ≥3 adverse events (AEs) occurred in 58.4% of pts; 11.6% discontinued Tx due to AEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 18 pts (6.7% [G1, n=6; G2, n=11; G5, n=1]). Conclusions: This is the first tumor-agnostic global study of T-DXd in a broad range of HER2-expressing solid tumors. T-DXd showed encouraging ORR, particularly in pts with IHC 3+ expression, durable clinical benefit, and a manageable safety profile in this heavily pretreated population. These interim results show T-DXd to be a potential new Tx option for pts with HER2-expressing solid tumors. Clinical trial information: NCT04482309 . [Table: see text]
Phase 3 THOR study: Results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt).
Authors: Loriot Yohann , Matsubara Nobuaki , Park Se Hoon , Huddart Robert A , Burgess Earle F , Houede Nadine , Banek Severine , Laguerre Brigitte , Guadalupi Valentina , Ku Ja Hyeon , Triantos Spyros , Akapame Sydney , Deprince Kris , Mukhopadhyay Sutapa , Siefker-Radtke Arlene O.
Published: June 2023

LBA4619

Background: FGFRalt are observed in ~20% of pts with mUC. Erda is an oral selective pan-FGFR tyrosine kinase inhibitor granted accelerated approval to treat locally advanced or mUC in adults with susceptible FGFR3/2alt who have progressed after platinum-containing chemo. THOR (NCT03390504), a randomized phase 3 study, assessed whether erda provided a survival advantage vs investigator’s choice of chemo in pts with mUC who progressed after 1 or 2 prior treatments, including an anti-PD-(L)1 agent. Methods: Pts (≥18 y) with unresectable advanced/mUC and select FGFR3/2alt (mutations/fusions), ECOG performance status 0-2, adequate organ function, progression on/after prior systemic therapy (tx) that included an anti-PD-(L)1 agent, and ≤2 prior lines of tx were randomized 1:1 to receive erda (8 mg with pharmacodynamically guided uptitration to 9 mg on day 14) QD or investigator’s choice of chemo (docetaxel or vinflunine) Q3W until disease progression or intolerable toxicity. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: 266 pts were randomized: 136 pts assigned to erda, 130 to chemo. In all pts, median age was 67 y; 30% had 1 prior line of tx, 70% had 2 prior lines; 74% had visceral metastases; 90% were PD-L1 low (CPS <10). Median follow-up was 15.9 mo. The primary endpoint of the study was met, with erda significantly increasing OS and reducing the risk of death by 36%; median OS was 1 y (Table). These data met predefined stopping criteria for superiority. Erda also significantly improved median PFS (5.6 vs 2.7 mo) and ORR (46% vs 12%) vs chemo. No new safety signals were seen. Serious treatment-related adverse events (TRAEs) were observed in 13% and 24% of pts with erda and chemo, respectively, and grade (Gr) 3/4 TRAEs were observed in 46% and 46% of pts with erda and chemo, respectively. TRAEs leading to death were reported in 1 and 6 pts with erda and chemo, respectively. More TRAEs leading to dose reduction were observed with erda (66%) vs chemo (21%); 8% and 13% of pts had TRAEs leading to discontinuation of erda and chemo, respectively. Central serous retinopathy occurred in 23 pts (17%) with erda (Gr 1-2, 20 pts). Conclusions: In pts with FGFRalt advanced/mUC after prior treatment with PD-(L)1, erda significantly improved OS, PFS, and ORR vs investigator’s choice of chemo. Erda toxicity was consistent with the known safety profile. These results support the role of erda to treat pts with FGFRalt mUC after PD-(L)1 tx. Clinical trial information: NCT03390504 . [Table: see text]
Nine-weeks versus one-year trastuzumab for early-stage HER2+ breast cancer: 10-year update of the Short-HER phase III randomized trial.
Authors: Conte Pier Franco , Bisagni Giancarlo , Piacentini Federico , Sarti Samanta , Minichillo Santino , Anselmi Elisa , Aieta Michele , Gebbia Vittorio , Schirone A , Musolino Antonino , Garrone Ornelia , Beano A , Rimanti Anita , Giotta Francesco , Turletti Anna , Dieci Maria Vittoria , Vicini Roberto , Balduzzi Sara , D'Amico R , Guarneri Valentina
Published: June 2023

LBA637

Background: The ShortHER trial is a phase III non-inferiority, randomized trial comparing 9 weeks (short arm) versus 1 year (long arm) of adjuvant trastuzumab combined with chemotherapy in HER2+ eBC patients. The first primary end point of the study was the event-driven analysis of disease-free survival which was achieved in 2017, presented at ASCO 2017 and published in Annals of Oncology in 2018. The HR was 1.13 (90% CI 0.89-1.42) and the non-inferiority could not be claimed as the upper border of CI crossed the upper limit of 1.29 chosen as non-inferiority margin. According to a pre-planned Bayesian analysis, the probability that the short arm was not inferior to the standard one was 80%. Methods: 1254 HER2+ early breast cancer patients were stratified according to nodal status and randomized. Median age was 55 years (range 25-78); 672 (54%) patients were node negative, 383 (30%) with 1-3 positive nodes, 198 (16%) 4 or more positive nodes. At the time of the event-driven analysis, median follow up was 6 years, 200 DFS events and 78 deaths were reported. Here we report the overall survival,+ which was the second co-primary end point, updated DFS and outcomes according to nodal status. Results: Median follow-up is now 9 years, 248 DFS events and 116 deaths have been reported. The 10 year DFS is 77% in the long arm and 78% in the short arm (HR 1.06; 90% CI 0.86-1.31). The 10-year OS is 89% in the long arm and 88% in the short arm (HR 1.15; 90% CI 0.85-1.56). The DFS and OS data overall and by nodal status are summarized in the table below. Conclusions: At a median follow-up of 9 years, the ShortHER trial shows that 1 year trastuzumab is still the standard treatment for HER2+ eBC patients as non-inferiority cannot be claimed in terms of DFS or OS. Numerically however, the differences for the patients at low risk (N0) or intermediate risk (N 1-3) is negligible and patients with 4 or more positive lymph nodes have a clear benefit with 1 year trastuzumab. I. This long-term date can reassure clinicians if, for any reason a patient at low/intermediate risk has to stop trastuzumab and, more important, might facilitate access to a far less expensive treatment to the thousands of patients worldwide who cannot afford the cost of one year of trastuzumab. Clinical trial information: NCT00629278 . [Table: see text]
Beta-Blocker Use Is Associated With Worse Relapse-Free Survival in Patients With Head and Neck Cancer
Authors: Chen Hannah Y. , Zhao Weilu , Na'ara Shorook , Gleber-Netto Frederico O. , Xie Tongxin , Ali Shahrukh , Thompson Zachary M. , Buell Jane , Stafford Haleigh , Nagarajan Priyadharsini , Davies Michael , Wong Michael K. , Migden Michael R. , Sharma Padmanee , Myers Jeffrey N. , Gross Neil D. , Amit Moran
Published: June 2023

PURPOSE

Although beta-blockers (BBs) have been hypothesized to exert a beneficial effect on cancer survival through inhibition of beta-adrenergic signaling pathways, clinical data on this issue have been inconsistent. We investigated the impact of BBs on survival outcomes and efficacy of immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC), non–small-cell lung cancer (NSCLC), melanoma, or squamous cell carcinoma of the skin (skin SCC), independent of comorbidity status or cancer treatment regimen.

METHODS

Patients (N = 4,192) younger than 65 years with HNSCC, NSCLC, melanoma, or skin SCC treated at MD Anderson Cancer Center from 2010 to 2021 were included. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were calculated. Kaplan-Meier and multivariate analyses adjusting for age, sex, TNM staging, comorbidities, and treatment modalities were performed to assess the effect of BBs on survival outcomes.

RESULTS

In patients with HNSCC (n = 682), BB use was associated with worse OS and DFS (OS: adjusted hazard ratio [aHR], 1.67; 95% CI, 1.06 to 2.62; P = .027; DFS: aHR, 1.67; 95% CI, 1.06 to 2.63; P = .027), with DSS trending to significance (DSS: aHR, 1.52; 95% CI, 0.96 to 2.41; P = .072). Negative effects of BBs were not observed in the patients with NSCLC (n = 2,037), melanoma (n = 1,331), or skin SCC (n = 123). Furthermore, decreased response to cancer treatment was observed in patients with HNSCC with BB use (aHR, 2.47; 95% CI, 1.14 to 5.38; P = .022).

CONCLUSION

The effect of BBs on cancer survival outcomes is heterogeneous and varies according to cancer type and immunotherapy status. In this study, BB intake was associated with worse DSS and DFS in patients with head and neck cancer not treated with immunotherapy, but not in patients with NSCLC or skin cancer.
The Effects of Intraoperative Methadone on Postoperative Pain Control in Pediatric Patients: A Scoping Review
Authors: Azamfirei Razvan , Procaccini Dave , Lobner Katie , Kudchadkar Sapna R.
Published: June 2023

Inadequate perioperative pain control has deleterious effects on children’s development and can lead to heightened pain experiences and the avoidance of future medical procedures. Reports of perioperative use of methadone in children are increasing, as it has a favorable pharmacodynamic profile; however, the effectiveness of methadone in reducing postoperative pain has not been established. We, therefore, aimed to provide a scoping review of the literature comparing the effect of intraoperative methadone versus other opioids on postoperative opioid consumption, pain scores, and adverse events in pediatric patients. We identified studies in PubMed, Scopus, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to January 2023. Postoperative opioid consumption, pain scores, and adverse events were extracted for analysis. We screened 1864 studies, of which 83 studies were selected for full-text review. Five studies were included in the final analysis. Postoperative opioid consumption was decreased overall in children who received methadone compared to those who did not. The majority of studies indicated that methadone was superior to other opioids in reported pain scores, while the frequency of adverse events was similar between the groups. Although the data reviewed highlight a potential benefit of intraoperative methadone in pediatric patients, 4 of the 5 studies had serious methodological concerns. Thus, we cannot make strong recommendations for the regular use of methadone in the perioperative setting at this time. Our results highlight the need for large, well-designed randomized trials to fully evaluate the safety and efficacy of intraoperative methadone in diverse pediatric surgical populations.
Gift or Weapon? Reproductive Decision, the Phenomenology of Pregnancy, and Alien Language in Denis Villeneuve's Arrival
Authors: Morgenstern Naomi
Published: June 2023

This essay analyzes Denis Villeneuve's 2016 film, Arrival, and elucidates its strikingly original meditation on the ethics of reproduction and the relationships between and among embodied maternal subjectivity, language, and temporality. Drawing on deconstructive theories of language and relationality as well as on the writing of scholars working at the intersection of reproductive biology and feminist philosophy, the essay argues that Arrival uses some of the generic features of science fiction cinema (alien encounter and time travel) to articulate a feminist and posthumanist philosophy of relation and care. Focusing on the film's language of risk, danger, contamination, and even social disintegration, Arrival prompts us to consider how a particularly suggestive account of the maternal-fetal relationship, and of the process of fostering and becoming a relationally determined being, simultaneously engages with the fraught question of reproductive choice and reproductive justice in our contemporary moment. Meditating on the film's visual, sonic, and conceptual representations of the “placental wall” and of the “parasitical” structure of pregnancy, the essay shows how Arrival parallels feminist readings of the materiality of pregnancy that deconstruct the self-possessed or “virile” subject of patriarchal individualism.
Gastrostomy Sequence With Ventriculoperitoneal Shunting—Does It Matter?
Authors: Khalid Syed I. , Deysher Daniel , Khilwani Harsh , Mirpuri Pranav , Thomson Kyle , Maynard Marquis , Mehta Ankit I.
Published: June 2023

BACKGROUND:

Neurological injury requiring ventriculoperitoneal shunt (VPS) placement often necessitates gastrostomy for nutritional support. The sequence of these procedures is debated over concerns for shunt infection and displacement requiring revisional surgery as a consequence of gastrostomy.

OBJECTIVE:

To determine the optimal sequence of VPS shunt and gastrostomy tube placement in adults.

METHODS:

In an all-payer database, adult patients undergoing gastrostomy and VPS placement were identified within 15 days between January 2010 and October 2021. Patients were categorized as receiving gastrostomy before, on the same day as, or after shunt placement. The primary outcomes of this study were rates of revision and infection. All outcomes were evaluated within 30 months after index shunting.

RESULTS:

In total, 3015 patients were identified as undergoing VPS and gastrostomy procedures within 15 days. After a 1:1:1 match, 1080 patient records were analyzed. Revision rates at 30 months were significantly lower among patients who received VPS and gastrostomy procedures on the same day compared with gastrostomy after VPS (odds ratio [OR] 0.61, 95% CI 0.39-0.96). In addition, patients who received gastrostomy before VPS compared with those after had lower revision rates (OR 0.61, 95% CI 0.39-0.96) and infection (OR 0.46, 95% CI 0.21-0.99). No significant differences were noted in mechanical complication or shunt displacement rates.

CONCLUSION:

Patients requiring VPS and gastrostomy may benefit from undergoing both procedures concurrently or with gastrostomy before VPS placement, secondary to lower revision rates. Patients undergoing gastrostomy before VPS have the added benefit of decreased infection rates.
DNA methylation dynamic in male rat germ cells during gametogenesis
Authors: El Omri-Charai Rhizlane , Gilbert Isabelle , Prunier Julien , Desmarais Rebecka , Ghinet Mariana Gabriela , Robert Claude , Boissonneault Guylain , Delbes Géraldine
Published: June 2023

In mammals, a near complete resetting of DNA methylation (DNAme) is observed during germline establishment. This wave of epigenetic reprogramming is sensitive to the environment, which could impair the establishment of an optimal state of the gamete epigenome, hence proper embryo development. Yet, we lack a comprehensive understanding of DNAme dynamics during spermatogenesis, especially in rats, the model of choice for toxicological studies. Using a combination of cell sorting and DNA methyl-seq capture, we generated a stage-specific mapping of DNAme in nine populations of differentiating germ cells from perinatal life to spermiogenesis. DNAme was found to reach its lowest level at gestational day 18, the last demethylated coding regions being associated with negative regulation of cell movement. The following de novo DNAme displayed three different kinetics with common and distinct genomic enrichments, suggesting a non-random process. DNAme variations were also detected at key steps of chromatin remodeling during spermiogenesis, revealing potential sensitivity. These methylome datasets for coding sequences during normal spermatogenesis in rat provide an essential reference for studying epigenetic-related effects of disease or environmental factors on the male germline.
Muscle force–length dynamics during walking over obstacles indicates delayed recovery and a shift towards more ‘strut-like’ function in birds with proprioceptive deficit
Authors: Schwaner M. Janneke , Gordon Joanne C. , Biewener Andrew A. , Daley Monica A.
Published: June 2023

Recent studies of in vivo muscle function in guinea fowl revealed that distal leg muscles rapidly modulate force and work to stabilize running in uneven terrain. Previous studies focused on running only, and it remains unclear how muscular mechanisms for stability differ between walking and running. Here, we investigated in vivo function of the lateral gastrocnemius (LG) during walking over obstacles. We compared muscle function in birds with intact (iLG) versus self-reinnervated LG (rLG). Self-reinnervation results in proprioceptive feedback deficit due to loss of monosynaptic stretch reflex. We tested the hypothesis that proprioceptive deficit results in decreased modulation of EMG activity in response to obstacle contact, and a delayed obstacle recovery compared with that for iLG. We found that total myoelectric intensity (Etot) of iLG increased by 68% in obstacle strides (S 0) compared with level terrain, suggesting a substantial reflex-mediated response. In contrast, Etot of rLG increased by 31% in S 0 strides compared with level walking, but also increased by 43% in the first post-obstacle (S +1) stride. In iLG, muscle force and work differed significantly from level walking only in the S 0 stride, indicating a single-stride recovery. In rLG, force increased in S 0, S +1 and S +2 compared with level walking, indicating three-stride obstacle recovery. Interestingly, rLG showed little variation in work output and shortening velocity in obstacle terrain, indicating a shift towards near-isometric strut-like function. Reinnervated birds also adopted a more crouched posture across level and obstacle terrains compared with intact birds. These findings suggest gait-specific control mechanisms in walking and running.
Which came first: the chicken, the egg, or guanine?
Authors: Kankia Besik
Published: June 2023

The main goal of the origin of life (OoL) hypothesis is to reconstruct the missing link between the primordial soup and the extant biology. However, the OoL itself is just the initial part of the link representing the bootstrapping operation of Darwinian evolution. The rest of the link is the emergence of the evolution to the present day primary biological system—the ribosome-based translation apparatus. A valid hypothesis must (i) not invoke Darwinian evolution in the bootstrapping and (ii) transform the ab initio life form into the translation apparatus without violating the principle of continuity (i.e., only incremental steps without foresight). Currently, no such hypothesis exists. Here, I discuss the Quadruplex World hypothesis, which fully complies with these requirements and suggests a spontaneous emergence of the ab initio life form. The spontaneity of OoL arises from the physicochemical properties of guanine monomers in a manner of causal determinism: each step of the process (i.e., scaffolding, polymerization, and folding) is caused by the most recent past step such that in the end only the specific 3D architecture forms. The architecture (i) has a length-independent folding pattern; (ii) can play the role of the predecessor of tRNA and single-handedly conduct a primitive form of translation; and (iii) can evolve into the extant translation apparatus without any paradoxes.
Efficacy and safety of mizoribine in comparison with cyclophosphamide for treatment of lupus nephritis: Protocol for a multi-center, open-label, randomized controlled trial
Authors: Dong Zheyi , Zhou Jianhui , Wang Yong , Sun Shiren , He Yani , Ni Zhaohui , Lin Hongli , Sun Xuefeng , Zhang Li , Chen Xiangmei
Published: June 2023

Background: Monthly intravenous cyclophosphamide (IVCY) is a widely accepted induction therapy for lupus nephritis (LN) because this regimen balances the time needed for renal remission with the risk of adverse events. However, IVCY is associated with numerous severe toxicities. Mizoribine (MZR) was originally used as an antibiotic against Candida albicans, but researchers found it had strong immunosuppressive activity in various animal models. Previous clinical trials also examined the efficacy of MZR as an immunosuppressant, and it has been used for treatment of LN in Japan since 1990. We will conduct a phase 3 study in China to evaluate the efficacy and safety of oral MZR in comparison with standard IVCY in patients with LN.

Methods: This study will be a multi-center, randomized, controlled, open-label clinical trial that consists of a screening period (seven days) followed by a treatment period (52 weeks). After screening, all eligible subjects will be randomized to an MZR or IVCY group in a 1:1 ratio. Then, subjects will initially receive methylprednisolone pulse therapy (0.5 g/day) for three days, followed by the study drug (MZR or CY) with oral corticosteroid therapy from visit two (day four). The efficacy and safety of oral MZR in comparison with standard IVCY will be determined.

Discussion: This paper describes the protocol of a multi-center, open-label, randomized controlled trial that compares the efficacy and safety of MZR with IVCY for treatment of LN. The results may help determine whether LN should be considered an indication for this drug in China.

Trial registration: ClinicalTrials.gov register, NCT02256150. Registered 2014-10-01. The protocol version number is 1.3 (2016-08-30).
Sociodemographic and clinical characteristics of hospital admissions for COVID-19: A retrospective cohort of patients in two hospitals in the south of Brazil
Authors: Jesus Edna Ribeiro de , Boell Julia Estela Willrich , Reckziegel Juliana Cristina Lessmann , Vaz Rafael Sittoni , Goulart Marco Aurélio , Peluso Flávia Marin , Nogueira Tiago da Cruz , Ávila Márcio Costa Silveira de , Malkiewiez Michelle Mariah , Schmidt Catiele Raquel , Weissenberg Vanessa Cruz Corrêa , Piccolin Millena Maria , Charão Junior Walmiro Martins , Lorenzini Elisiane
Published: June 2023

Background: This database aims to present the sociodemographic and clinical profile of a cohort of 799 patients hospitalized with coronavirus disease 2019 (COVID-19) in two hospitals in southern Brazil.

Methods: Data were collected, retrospectively, from November 2020 to January 2021, from the medical records of all hospital admissions that occurred from 1 April 2020 to 31 December 2020. The analysis of these data can contribute to the definition of the clinical and sociodemographic profile of patients with COVID-19.

Data description: This dataset covers 799 patients hospitalized for COVID-19, characterized by the following sociodemographic variables: sex, age group, race, marital status and paid work. The sex variable was collected as sex assigned at birth from medical records data. Clinical variables included: admission to clinical ward, hospitalization in the Intensive Care Unit, COVID-19 diagnosis, number of times hospitalized due to COVID, hospitalization time in days and risk classification protocol. Other clinical variables include: pulmonary impairment; patients ventilation pattern; high-flow oxygen mask; pulmonary thromboembolism; cardiovascular disease; pulmonary sepsis; influenza exam results. Other health problems: diabetes, systemic arterial hypertension, chronic obstructive pulmonary disease, obesity, tabaco smoking, asthma, chronic kidney disease, overweight, vascular accident, sedentary lifestyle, HIV/AIDS, cancer, Alzheimer's disease, Parkinson's disease.

Conclusions: The analysis of these data can contribute to the definition of the clinical and sociodemographic profile of patients with COVID-19. Thus, a great social impact is demonstrated when databases are published. Open data accelerates the research process, facilitates reuse and enriches datasets, in addition to optimizing the application of public resources, that is, enabling more use of the same investment.