bluuebunny/crossref_metadata_2025 huggingface dataset:
nextHERIZON: A phase 2 study of HER-Vaxx, a HER2-targeting peptide vaccine, in combination with chemotherapy or pembrolizumab in patients with HER2 metastatic or advanced gastric/gastroesophageal adenocarcinoma that progressed on or after trastuzumab treatment.
Authors: Price Timothy Jay , Chong Leslie Mi Ok , Ede Nicholas , Nixon Bonnie , Withana Nimali , Yavrom Sharon , Selvaggi Giovanni , Good Anthony J.
Published: January 2023

TPS481

Background: HER-Vaxx is a B-cell peptide vaccine composed of a fusion of 3 epitopes from the extracellular domain of HER2/neu conjugated to CRM197 with the adjuvant Montanide. Results from a phase 1b study revealed that active immunization with HER-Vaxx was well tolerated and induced HER2-dose dependent immune responses corresponding to tumor reduction in advanced gastric cancer (GC) or gastroesophageal adenocarcinoma (GEA) (Wiedermann, 2021). A phase 2 study, HERIZON, comparing HER-Vaxx plus standard chemotherapy or chemotherapy alone is currently enrolling. Pre-clinical data demonstrated a synergistic effect with combination of HER2 and PD-1 vaccines and 90% tumor growth inhibition (Kaumaya, 2020). Ramucirumab plus paclitaxel is an approved second-line treatment for patients with GC or GEA who have failed first-line treatment chemotherapy or trastuzumab (TRA) (Wilke, 2014). The nextHERIZON study seeks to evaluate the clinical benefit of adding HER-Vaxx to ramucirumab plus paclitaxel or pembrolizumab, following progression on TRA. Methods: nextHERIZON is phase 2, open-label, non-comparative, double arm, 2-stage design study in patients with confirmed AGC and HER2 overexpression following progression on or after TRA. Arm assignment depends on prior PD-1/PD-L1 inhibitor treatment. Arm 1 will receive HER-Vaxx + ramucirumab and paclitaxel. Arm 2 will receive HER-Vaxx + pembrolizumab. Up to 55 patients will be enrolled in each arm which includes a safety run-in phase. Arms will be analyzed independently. The key inclusion criteria are: patients ³ 18 year of age; ECOG 0 or 1; minimum life expectancy of 3 months; progressed on or after TRA; confirmed HER2 overexpression; at least one measurable lesion; adequate hematologic and organ function. Key exclusion criteria include previous treatment with trastuzumab-deruxtecan or any other anti-HER2 therapy other than trastuzumab. Arm 2 excludes prior therapy with anti- PD-1, PD-L1 or PD-L2 agents. The co-primary endpoints are safety and objective response rate (RECIST 1.1). Secondary objectives are efficacy and survival measures. HER-Vaxx is administered by intramuscular (IM) injection on Day 1, Day 15, and Day 29 and on Day 1 of each 2nd or 3rd cycle depending on arm. Dose-limiting toxicity (DLT) window is 29 days on treatment. Tumor assessment is evaluated at Day 43 then every 6 weeks until progression or withdrawal. This study is currently enrolling patients in Australia and US (Q1 2023). Clinical trial information: NCT05311176 .
An open-label, multi-center phase IIIb study of durvalumab and tremelimumab as first-line treatment in patients with unresectable hepatocellular carcinoma (TREMENDOUS study).
Authors: Fan Jia , Qin Shukui , Sun Hui-Chuan
Published: January 2023

TPS628

Background: Hepatocellular carcinoma (HCC) is of high incidence and mortality rate in China, with nearly half of them are diagnosed as advanced or metastatic stage at the initial diagnosis. First-line treatment options for patients with advanced disease previously included tyrosine kinase inhibitors and immune checkpoint inhibitors in combination with vascular endothelial growth factor. Recently, the phase III HIMALAYA trial investigated the STRIDE regimen, tremelimumab 300mg × 1 dose and durvalumab 1500mg every 4 weeks, compared to sorafenib in previously untreated locally advanced or metastatic HCC patients, and resulted in significantly improved overall survival (OS) (16.4 mos vs 13.8mos, HR=0.78) and a well-tolerated safety profile (≥grade 3 treatment-related adverse events 25.8% vs 36.9% ). Notably, the HIMALAYA trial did not enroll subject from mainland China and excluded patients with class Child-Pugh B liver dysfunction or ECOG performance status (PS) 2. We hypothesize the STRIDE regimen will be safe and well tolerated in Chinese patients with locally advanced or metastatic HCC with Child-Pugh class A or B liver dysfunction or ECOG PS 0-2. In addition, the study will also assess efficacy and explore biomarkers. Methods: This will be an open label, multi-center phase IIIb study investigating the safety and efficacy of the STRIDE regimen in Chinese unresectable HCC patients without prior systemic therapy. Patients with Child-Pugh A liver dysfunction and ECOG PS 0-1 will be enrolled in cohort 1, while patients with Child-Pugh B liver dysfunction or ECOG PS 2 will be enrolled in cohort 2. Patients with main portal vein tumor thrombosis (Vp4), clinically significant ascites or hepatic encephalopathy, or active or prior documented gastrointestinal bleeding within 12 months will be excluded. We plan to enroll 300 patients with the primary endpoint of grade 3-5 adverse event (AE) rate by CTCAE v5.0 and adverse events of special interest (AESI). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), OS, OS rate at 6 months and 12 months. Patients of both cohorts will receive a single dose of tremelimumab 300 mg and durvalumab 1500 mg at Cycle 1 (Week 0), followed by durvalumab 1500 mg monotherapy every 4 weeks until confirmed disease progression or unacceptable toxicity. Archival or fresh tumor biopsy will be required at baseline. The trial is currently screening eligible subjects. Clinical trial information: CTR20222433 .
Phase II trial of durvalumab (MEDI4736) with/without tremelimumab for advanced hepatocellular carcinoma after palliative hypofractionated radiotherapy.
Authors: Andemicael Luchia , Chang Hewitt , Anwar Moshiur Mekhail , Bauer Kelly , Gordan John , Johnson Jamese , Keenan Bridget P , Venook Alan P. , Wang Chia-Ching Jackie , Zhang Karen , Fong Lawrence , Kelley Robin Kate , Feng Mary Uan-Sian
Published: January 2023

TPS630

Background: Hepatocellular Carcinoma (HCC) is among the most common types and leading causes of cancer death globally, and the incidence is on the rise. For patients with advanced hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICI) in combination with anti-angiogenic agents or other ICI improve survival compared with tyrosine kinase inhibition. Though ICI-based regimens can achieve prolonged responses in some patients and prolong overall survival, only a subset of patients achieve durable responses. There is an urgent need for strategies to overcome primary and acquired resistance. Many of these patients have symptomatic sites of disease which could benefit from local palliative radiotherapy. Radiotherapy also has the potential to elicit an abscopal immune response when combined with ICI. We hypothesize that combining Radiation Treatment (RT) with Durvalumab or the combination of Durvalumab + Tremelimumab (combination D+T in STRIDE regimen showed OS improvement in HIMALAYA trial in 1st line HCC) will achieve a meaningful response rate in advanced HCC patients after progression on other ICI-based therapies. Methods: This is an open label, single center, two-arm, non-comparative phase II trial. Key eligibility criteria are; histologically-diagnosed HCC with progression during or after prior PD-(L)1 checkpoint inhibitor immunotherapy and at least 1 RECIST 1.1-measurable tumor present which has not received RT or other local therapy prior to enrollment, ECOG 0-1, and Child Pugh score of A, B7, or B8. Patients are assigned sequentially to either single-agent durvalumab initiated starting 3 to 10 days after completing RT (25 Gy in 5 fractions to 1-5 sites of disease), at fixed dose of 1500 mg IV every 28 days, or a single fixed dose of tremelimumab of 300 mg IV administered on Day 1, initiated within 3-10 days of completing RT, in combination with durvalumab at fixed dose of 1500 mg IV every 28 days; for up to 24 months or until confirmed radiographic progression. The primary end point is overall response rate (ORR) and secondary endpoints include proportion of participants with adverse events, overall survival, progression free survival and duration of response. Exploratory endpoints include profiling of peripheral blood mononuclear cell immune cells and plasma biomarkers. We plan to accrue 30 patients to this study, 15 to each Arm, to evaluate ORR which would allow us to detect at least a 20% ORR, which would be a clinically meaningful improvement in efficacy in this population with otherwise poor treatment options assuming a statistical power of 87% and a directional 5% statistical significance level based upon an exact binomial test. The trial is open and enrolling. Clinical trial information: NCT04430452 .
A randomized, multi-center phase III trial of adjuvant chemotherapy with gemcitabine and capecitabine (GemCap) compared to capecitabine (Cap) alone in curatively resected biliary tract cancer (BilGemCap Study): KCSG HB20-14.
Authors: Park Joon Oh , Park Joon Seong , Lee Choong-kun , Chon Hong Jae , Choi Sae Byeol , Hwang Dae Wook , Oh Do-Youn , Lee Myung Ah , Jang Jin-Young , Ryoo Baek-Yeol
Published: January 2023

TPS633

Background: Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage; thus, only 20% of the patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. Recent phase 3 trials using single agent such as Cap or S1 support the role of adjuvant chemotherapy as standard of care in patients with resected BTCs, but the efficacy still needs to be further improved. Therefore, we designed a randomized, multi-center, phase 3 trial comparing GemCap with Cap in curatively resected BTC patients. Methods: The primary endpoint is 24-month disease-free survival (DFS) and secondary endpoints are overall survival (OS), quality of life (QOL), toxicities and exploratory biomarker analysis. Referring to the recent results of BILCAP study, the sample size calculation is based on the assumption that the 24-month DFS would be 50% in the Cap arm, and that treatment with GemCap would improve the 24-months DFS by 10%, from 50% to 60%. As such, 490 patients and 337 events are needed to detect a HR of 0.737, with a two-sided significance level of 5% and 80% power. Patients aged 19 years or older with macroscopically resected intra- or extrahepatic cholangiocarcinoma and muscle-invasive gallbladder cancer (T2-4 or N1-2, M0) are eligible. The Eastern Cooperative Oncology Group (ECOG) performance status have to be 0-1, and adequate renal, hematological, and liver function is required. Patients who had not completely recovered within 12 weeks from surgery or who had previous history of chemotherapy or radiotherapy for BTC are also excluded. Patients are randomly assigned 1:1 to the GemCap arm or the Cap arm, stratified by LN status (N0 vs. N+), resection status (R0 vs. R1) and primary site. After randomization, either oral Cap (1250 mg/m²) twice a day on days 1 to 14 of a 3-weekly cycle (8 cycles), or oral Cap (830 mg/m²) twice a day on days 1 to 21 plus Gem (830 mg/m²) on days 1, 8 and 15 of a 4-weeky cycle (6 cycles) are given. As of September 2022, 147 patents have been randomized to each arm, and updated study status will be presented. This is a collaborative study with Korean Cancer Study Group (KCSG) and Korean Pancreas Surgery Club (KPSC), supported by a grant from the National R&D Program for Cancer Control through the National Cancer Center (NCC) funded by the Ministry of Health & Welfare, Republic of Korea (HA22C0053). This is prospectively registered on ClinicalTrials.gov, NCT0005056. Clinical trial information: NCT0005056 .
Trial in progress: A phase 2/3 randomized, controlled study of CTX-009 in combination with paclitaxel versus paclitaxel alone in adult patients with unresectable advanced, metastatic or recurrent biliary tract cancers who have received one prior systemic chemotherapy regimen.
Authors: Fontaine Marilyn , Pilgrim Sarah , Schuetz Thomas
Published: January 2023

TPS640

Background: CTX-009 is a recombinant bispecific antibody that binds both delta-like ligand-4 (DLL4) and vascular endothelial growth factor A (VEGF-A). The antibody simultaneously inhibits the DLL4-Notch 1 and VEGF A-VEGF receptor signaling pathways. Presently, there is no consensus second-line therapy for patients with Biliary Tract Cancer (BTC) in whom first-line therapy has failed. In a Phase 1b study of CTX-009 in combination with paclitaxel, there were 4 patients with cholangiocarcinoma enrolled, and 2 of these 4 patients (both received CTX-009 at 10mg/kg + paclitaxel) had confirmed PRs with declines of 41.4% and 61.6% in their linear tumor burden from the baseline. Both of these patients had multiple prior therapies, and were on study for more than a year, with durable responses for more than 9 months each. Based on that observation, an adaptive Phase 2 cohort was added to the Phase 1b Study. There are currently 9 confirmed PRs among 24 patients treated for a 37.5% overall response rate in the ongoing Phase 2 Study of CTX-009 in combination with paclitaxel in patients with BTC treated in the second- or third-line setting. While there is anecdotal data suggesting that taxanes may have activity in BTC, the contribution of CTX-009 needs to be confirmed in a randomized study. Methods: CTX-009 is being evaluated in an open-label, randomized, controlled study in patients with previously treated, advanced or metastatic BTC. 120 patients will be randomized in a 2:1 ratio to receive either CTX-009 plus paclitaxel or paclitaxel alone. The stratification factors to be used at randomization include sex, presence of disease inside the liver only (intrahepatic cholangiocarcinoma) vs. outside the liver (all extrahepatic BTC or metastatic disease), and Eastern Cooperative Oncology Group (ECOG) Performance status (0 vs. 1). Patients will be treated in 28-day cycles, with CTX-009 administered at 10 mg/kg IV on Day 1 and 15, and paclitaxel administered at 80 mg/m2 on days 1, 8, and 15. The primary objective of the study is to assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone, as measured by Overall Response Rate (ORR) assessed by an Independent Central Radiology (ICR) review. Key secondary objectives include overall survival, progression-free survival, and duration of response. The study is currently activating sites with first patient in expected to be enrolled in 2022. Clinical trial information: NCT05506943 .
Greco-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with rucosopasem (GC4711) in the treatment of locally advanced or borderline resectable nonmetastatic pancreatic cancer.
Authors: Aguilera Todd Anthony , Parikh Parag , Ghaly Maged , Hoffe Sarah E. , Herman Joseph M. , Caster Joseph Michael , Kim Dae Won , Costello James , Malafa Mokenge Peter , Beg Muhammad S. , Moser Elizabeth Charlotte , Kennedy Eugene Paul , Terry Kara , Kurman Michael
Published: January 2023

TPS766

Background: While treatment of pancreatic cancer has advanced, survival rates remain low. Stereotactic body radiotherapy (SBRT; high dose per fraction radiation) may exhibit improved clinical outcomes in locally advanced pancreatic cancer but carries potential gastrointestinal toxicity risks. Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically converts superoxide to hydrogen peroxide. Studies have shown that normal cells tolerate hydrogen peroxide fluxes better than cancer cells. As radiation response modifiers, dismutase mimetics have the potential to increase tumor control of SBRT without compromising radiation safety. In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT. Improvements versus placebo were also observed in local tumor control, time to metastases, and progression-free survival. Altogether, these data support the hypothesis that rucosopasem may improve survival and the benefit-risk ratio of SBRT by improving efficacy without increasing gastrointestinal toxicity. Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet. Approximately 160 patients will be randomized (approximately 35 sites) to receive rucosopasem 100 mg or placebo via IV infusion over 15 minutes, prior to each SBRT fraction (5 x 10 Gy). Patients judged to be resectable will undergo surgical exploration within 8 weeks after SBRT. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, locoregional control, time to metastasis, surgical resection rate, RO resection rate, best overall response, in-field local response, and safety (acute and late toxicities). Exploratory endpoints include PRO-CTCAE and CA19-9 normalization. This trial (NCT04698915) is now enrolling. Clinical trial information: NCT04698915 .
An adaptive approach to neoadjuvant therapy to maximize resection rates for pancreatic adenocarcinoma: A phase II trial.
Authors: Sohal Davendra , Kharofa Jordan , Olowokure Olugbenga Olanrele , Rojan Adam , Patel Sameer H. , Wilson Gregory C. , Sussman Jeffrey J. , Moreland Katie , Patra Krushna , Bogdanov Vladimir , Riall Taylor S , Zavros Yana , Shroff Rachna T. , Ahmad Syed A.
Published: January 2023

TPS771

Background: Curative treatment for potentially resectable (resectable or borderline resectable) pancreatic adenocarcinoma, despite recent advances, leads to only suboptimal outcomes. Recent US national cooperative group trials have demonstrated the safety and feasibility of neoadjuvant chemotherapy (PMID 33475684, PMID 35834226), and also show that the two frontline regimens, FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin) and gemcitabine/nab-paclitaxel (GnP), are comparable in this setting. Finally, ability to undergo resection remains the key driver of cure. Therefore, an approach that selects chemotherapy based on early response assessment, to maximize the probability of resection, is likely to improve curative outcomes. Methods: This is a phase II study intended to maximize the probability of surgical resection for pancreatic cancer. Key eligibility requirements include adult patients with a confirmed histopathologic diagnosis of pancreatic carcinoma or adenocarcinoma, an ECOG PS ≤ 1, resectable or borderline resectable disease by central radiology review, no prior therapy for index pancreatic cancer, and adequate bone marrow, liver and kidney function. Treatment includes 4 doses (~ 2 months total treatment time) of FOLFIRINOX (“Chemo1”). After a re-evaluation, using radiologic response, CA19.9 response, and chemotherapy toxicity, patients will either continue with “Chemo1” for another 4 cycles (8 doses) or switch to GnP (“Chemo2”) which will be administered for 4 cycles (12 doses, for ~4 month total treatment time), followed by surgical resection. Primary outcome will measure the proportion of patients undergoing surgical resection using historical dated compared to 32 patients in a current study with a time frame of 16 months. Using historical data, the expected proportion of patients undergoing resection is ~60%. The goal of this study is to increase this to 80% or higher. With a one-sided of 0.05 and power of 80%, 32 patients will be needed to demonstrate this difference. Key translational correlatives will include serial circulating tumor DNA assessment and extensive tumor molecular profiling. Clinical trial information: NCT04594772 .
Unpredictability and basin entropy
Authors: Daza Alvar , Wagemakers Alexandre , Sanjuán Miguel A. F.
Published: January 2023

The basin entropy is a simple idea that aims to measure the the final state unpredictability of multistable systems. Since 2016, the basin entropy has been widely used in different contexts of physics, from cold atoms to galactic dynamics. Furthermore, it has provided a natural framework to study basins of attraction in nonlinear dynamics and new criteria for the detection of fractal boundaries. In this article, we describe the concept as well as fundamental applications. In addition, we provide our perspective on the future challenges of applying the basin entropy idea to understanding complex systems.
Prevalence of Admission Hyponatremia in Patients With Diabetes Treated With and Without an SGLT2 inhibitor
Authors: Monnerat Sophie , Atila Cihan , Refardt Julie , Christ-Crain Mirjam
Published: January 2023

Context

Hyponatremia often reflects a free water excess. Sodium/glucose cotransporter 2 (SGLT2) inhibitors increase free water excretion through glucose-induced osmotic diuresis. In 2 randomized double-blind, placebo-controlled trials in patients with the syndrome of inappropriate antidiuresis (SIAD), we showed that empagliflozin increased plasma sodium concentration more effectively than placebo.

Objective

We hypothesized that long-term therapy with SGLT2 inhibitors might reduce the prevalence of hyponatremia on hospital admission.

Methods

In this retrospective analysis, we extracted data from adult patients with type 2 diabetes (T2DM) hospitalized at the University Hospital Basel between 2015 and 2020. Patients with an SGLT2 inhibitor on admission were matched 1:1 according to age, gender, diagnosis of heart failure, and principal diagnosis to patients without an SGLT2 inhibitor on admission. The primary outcome was the prevalence of hyponatremia (plasma sodium concentration corrected for glycemia <135 mmol/L) on admission.

Results

We analyzed 821 patients with T2DM treated with and 821 patients with T2DM without an SGLT2 inhibitor on admission. Hyponatremia prevalence on admission was 9.9% in the treated group, and 8.9% in the matched control group (P = .554), in other words, the risk for hyponatremia did not differ (multivariable adjusted odds ratio 1.08, 95% CI 0.72-1.44, P = .666). There was no difference in the median (interquartile range) plasma sodium concentration between the groups (treated 140 mmol/L [138-142], controls 140 mmol/L [138-142]; P = .1017).

Conclusion

Based on these retrospective findings, treatment with SGLT2 inhibitors does not prevent hyponatremia. However, prospective randomized data suggest their efficacy at a higher dosage in overt SIAD.
Role of Point-of-Care Ultrasound in Emergency Airway Management Outside the Operating Room
Authors: Khorsand Sarah , Chin Jeanette , Rice Jake , Bughrara Nibras , Myatra Sheila N. , Karamchandani Kunal
Published: January 2023

Tracheal intubation is one of the most frequently performed procedures in critically ill patients, and is associated with significant morbidity and mortality. Hemodynamic instability and cardiovascular collapse are common complications associated with the procedure, and are likely in patients with a physiologically difficult airway. Bedside point-of-care ultrasound (POCUS) can help identify patients with high risk of cardiovascular collapse, provide opportunity for hemodynamic and respiratory optimization, and help tailor airway management plans to meet individual patient needs. This review discusses the role of POCUS in emergency airway management, provides an algorithm to facilitate its incorporation into existing practice, and provides a framework for future studies.
Unlimited Discretion: How Unchecked Bureaucratic Discretion Can Threaten Abortion Availability
Authors: Heymann Orlaith , Bessett Danielle , Norris Alison , Hill Jessie , Czarnecki Danielle , Gyuras Hillary J. , Pensak Meredith , McGowan Michelle L.
Published: January 2023

Previous research has assessed the impact of state regulations on abortion clinics and patients, but how bureaucrats implement them is less understood and is increasingly important as states arbitrate abortion regulation. The authors conducted a case study of how bureaucrats use discretion to implement state regulations on abortion, focusing on two abortion facilities in southwest Ohio from 2010 to 2022. Ohio abortion facilities are required to obtain a written transfer agreement, despite it offering no demonstrable health or safety benefits. The authors find that state requirements for obtaining variances—a process that allows abortion facilities to operate without a written transfer agreement—have become exceedingly difficult to comply with. The authors show how state statutes and administrative law have enabled bureaucrats to wield unlimited discretion and enforce arbitrary requirements. This unlimited bureaucratic discretion and accompanying administrative burden exacerbated clinic instability and threatened abortion availability in southwest Ohio for almost a decade. As implementation and interpretation of abortion policy is increasingly left to state bureaucrats and civil servants following the Supreme Court's Dobbs decision, how bureaucrats use discretion will influence clinic stability and abortion availability. The authors posit that unlimited bureaucratic discretion may exert greater influence on abortion availability across the nation as states scramble to clarify and implement policies after Dobbs.
Mouse models of fragile X-related disorders
Authors: Willemsen Rob , Kooy R. Frank
Published: January 2023

The fragile X-related disorders are an important group of hereditary disorders that are caused by expanded CGG repeats in the 5′ untranslated region of the FMR1 gene or by mutations in the coding sequence of this gene. Two categories of pathological CGG repeats are associated with these disorders, full mutation alleles and shorter premutation alleles. Individuals with full mutation alleles develop fragile X syndrome, which causes autism and intellectual disability, whereas those with premutation alleles, which have shorter CGG expansions, can develop fragile X-associated tremor/ataxia syndrome, a progressive neurodegenerative disease. Thus, fragile X-related disorders can manifest as neurodegenerative or neurodevelopmental disorders, depending on the size of the repeat expansion. Here, we review mouse models of fragile X-related disorders and discuss how they have informed our understanding of neurodegenerative and neurodevelopmental disorders. We also assess the translational value of these models for developing rational targeted therapies for intellectual disability and autism disorders.
Complexity and self-organization in the evolution of cell polarization
Authors: Glazenburg Marieke M. , Laan Liedewij
Published: January 2023

Cellular life exhibits order and complexity, which typically increase over the course of evolution. Cell polarization is a well-studied example of an ordering process that breaks the internal symmetry of a cell by establishing a preferential axis. Like many cellular processes, polarization is driven by self-organization, meaning that the macroscopic pattern emerges as a consequence of microscopic molecular interactions at the biophysical level. However, the role of self-organization in the evolution of complex protein networks remains obscure. In this Review, we provide an overview of the evolution of polarization as a self-organizing process, focusing on the model species Saccharomyces cerevisiae and its fungal relatives. Moreover, we use this model system to discuss how self-organization might relate to evolutionary change, offering a shift in perspective on evolution at the microscopic scale.
Awareness of interventional radiology among medical students at KFU in Al-Hasa province
Authors: Al Mutairi Rahaf , Al Mulhim Mohammed , Bin mutreb Linah , Al Mutairi Mohammed , Hazem Mohammed
Published: January 2023

Background:

Interventional radiology (IR) is a branch of diagnostic radiology that performs minimally invasive procedure using image guided radiological techniques.

Methods:

To measure the awareness of IR between clinical-year medical students and medical interns at King Faisal University (KFU) in Al-Hasa province and the likelihood of medical students to enter IR in the future,

a cross-sectional study was performed between year 4 and 5 medical students  (clinical year students) and medical interns at KFU, Al-Hasa with the use of validated electronic questionnaire.

Results:

A total of 246 participants fulfilled the inclusion criteria of this study. The students were in clinical years: 54.9% were in their fourth year, 34.6% were in their fifth year, and 10.6% were interns. Approximately half of the responders (46.9%) think their knowledge regarding IR is poor. Lectures were the most frequently identified information source (33.3%). Around 48% of the participants had a satisfactory level of knowledge on interventional radiology.

Conclusion:

This study showed relatively poor awareness and knowledge toward IR among medical interns and clinical years medical students. To solve this issue, a number of strategies can be implemented, such as early inclusion of an interventional radiology course in the curriculum, IR symposiums, and IR awareness campaigns.
Bacterial pneumonia associated with multidrug-resistant Gram-negative pathogens: Understanding epidemiology, resistance patterns, and implications with COVID-19
Authors: Hammoudi Halat Dalal , Ayoub Moubareck Carole
Published: January 2023

The ongoing spread of antimicrobial resistance has complicated the treatment of bacterial hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Gram-negative pathogens, especially those with multidrug-resistant profiles, including Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Acinetobacter spp., are an important culprit in this type of infections. Understanding the determinants of resistance in pathogens causing pneumonia is ultimately stressing, especially in the shadows of the COVID-19 pandemic, when bacterial lung infections are considered a top priority that has become urgent to revise. Globally, the increasing prevalence of these pathogens in respiratory samples represents a significant infection challenge, with major limitations of treatment options and poor clinical outcomes. This review will focus on the epidemiology of HAP and VAP and will present the roles and the antimicrobial resistance patterns of implicated multidrug-resistant (MDR) Gram-negative pathogens like carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Enterobacterales (CRE), as well as colistin-resistant Gram-negative pathogens and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales. While emerging from the COVID-19 pandemic, perspectives and conclusions are drawn from findings of HAP and VAP caused by MDR Gram-negative bacteria in patients with COVID-19.
Microbial dynamics, risk assessment and sensory evaluation of metata ayib (traditional spiced fermented cottage cheese)
Authors: Adugna Mulugojjam , Andualem Berhanu
Published: January 2023

Introduction: Different traditional fermented foods and beverages made from various components are available in Ethiopia. Metata ayib, a traditional fermented dairy product, is created by blending ayib (Ethiopian cottage cheese) with different spices in a tightly covered container. Therefore, metata ayib is a ready-to-eat food. If it is handled with poor hygiene standards or is contaminated with potentially hazardous microorganisms, consuming it could be harmful. Therefore, the goal of this study was to assess the microbiological dynamics, organoleptic properties, and growth potential of some foodborne pathogens in metata ayib.

Methods: Three different kinds of metata ayib were made in a laboratory, and, using conventional microbiological methods, a microbiological examination was carried out during the fermentation process. Using 10 panellists, the sensory evaluation of the different types of metata ayib was conducted. The growth potential of selected pathogenic microorganisms on the preferred ready-to-eat metata ayib was then tested.

Results: Coliforms and Staphylococci species were not found in any type of metata ayib during the fermentation process. The counts of aerobic mesophilic bacteria (AMBC), lactic acid bacteria (LABC), yeast and  mold (YMC) in metata ayib that was made with black mustard seed and 12 other common spices were highest. Metata ayib prepared with black mustard seed and 12 additional common spices had significantly (P<0.05) higher sensory qualities in terms of taste than metata ayib prepared with red pepper or Ethiopian mustard seed, and 12 additional common spices. The growth capacity of Candida albicans in metata ayib made with black mustard seed and 12 other common spices showed greater resistance (24 h) than both E. coli (18 h) and S. aureus (6 h).

Conclusions: Care should be taken when handling fermented metata ayib. To improve the safety and health benefits of fermented metata ayib, it is preferable to inoculate it with possible probiotics.
The Avon Longitudinal Study of Parents and children ALSPAC G0 Partners: A cohort profile
Authors: Northstone Kate , Ben Shlomo Yoav , Teyhan Alison , Hill Amanda , Groom Alix , Mumme Mark , Timpson Nic , Golding Jean
Published: January 2023

ALSPAC is an ongoing population-based, observational study designed to investigate how genetic/environmental characteristics might influence the health/development of children and their parents. It has evolved to facilitate the measurement of many outcomes in the parental cohort. Pregnant women resident in Bristol, UK with expected dates of delivery between April 1991-December 1992 were eligible. 14,541 pregnancies were originally enrolled. Partners of the pregnant women were initially invited to take part by the women with formal enrolment of individuals since 2010. Data has been collected from 12,113 partners, with 3,807 formally enrolled. Data collected to date: 21 questionnaires, clinical follow up in 2012 (mean age: 53 years) and a family-based clinical follow-up currently ongoing (mean age: 63 years). Questionnaires asked about a wide range of environmental measures, physical/mental health and other phenotypic details including six questionnaires throughout the COVID-19 pandemic. Clinical measures include anthropometrics, blood pressure, body composition, cardiovascular health and a fasting blood sample. DNA has been extracted with genome-wide data available on >3,000 partners and exomes on ~1500 trios. The data contributes to one of the most deeply phenotyped birth cohorts in the world, providing trios of data and multi-generational information, and is fully accessible through a managed access process.
The genome sequence of the sea mat, Membranipora membranacea (Linnaeus, 1767)
Authors: Bishop John , Adkins Patrick , Wood Christine , Jenkins Helen ,   Marine Biological Association Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: January 2023

We present a genome assembly from an adult colony of Membranipora membranacea (the sea mat; Bryozoa; Gymnolaemata; Cheilostomatida; Membraniporidae). The genome sequence is 339 megabases in span. Most of the assembly (99.95%) is scaffolded into 11 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 14.7 kilobases in length.
Humani Generis & Evolution: A Report from the Archives
Authors: Kemp Kenneth W.
Published: January 2023

The opening of the archives for the pontificate of Pius XII makes it possible to see the history of the drafting of the encyclical Humani generis, the first document in which the universal magisterium of the Catholic Church addressed the question of evolution. Although its acknowledgment that the question of the evolutionary origin of the human body was, provisionally, theologically open generated no controversy at the drafting commission, the definitiveness of its reservations about monophyletic polygenism generated a disagreement resolved only by Pope Pius. Three incidents from the early 1950’s reinforce these conclusions about the proper interpretation of the encyclical.
Росия – міфічна краіна: компенсацийна роля уявлінь о росийскости в лемківскых культуровых текстах
Authors: Duć-Fajfer Helena
Published: January 2023

ROSJA – MITYCZNA KRAINA: KOMPENSACYJNA ROLA WYOBRAŻEŃ O ROSYJSKOŚCI W ŁEMKOWSKICH TEKSTACH KULTUROWYCH

W artykule została podjęta próba rozpoznania i przedstawienia konstruktów wyobraźniowych zawartych w łemkowskich tekstach kultury, głównie w piśmiennictwie, które odnoszą się do Rosji i rosyjskości. Kluczową rolę w tworzeniu konstruktów wyobrażeniowych odegrały uwarunkowania geopolityczne i kulturowe kształtowania się łemkowskiej tożsamości etnicznej. W tekście wyodrębnione zostają swoiste hipostazy rosyjskości, konkretyzujące się w łemkowskim dyskursie tożsamościowym: mit sprawiedliwego i dobrego cara, obrońcy prześladowanych Rusinów oraz wizja Rosji jako krainy dobrobytu. Przedstawione są osobowe/ personalne oraz tekstowe przykłady wpływu tych mitów. Opisane zostały utopie społeczne zbudowane na ich bazie. Wskazano też na konsekwencje politycznej interpretacji tych mitycznych i kulturowych obrazów dla losów całej społeczności łemkowskiej.
Examining the Presence of Dalit identity in Hindi Cinema
Authors: Wankhede Harish S.
Published: January 2023

A century of Bombay’s popular cinema has overtly celebrated the upper caste hero on screen. Major genres of Hindi cinema are stuffed with the Hindu-Brahmanical cultural values, social themes and political interests. The caste and question of Untouchability not even figured as the peripheral aspects of the cinema. The narratives revolve around certain abstract upper caste Hindu identities, divorced from the idea that in the actual Hindu social order caste distinctions play a crucial role. Bombay’s popular Hindi cinema though showcased artistic and intellectual agency by representing the problems of urban poor during its ‘Golden Age’ period, however the caste question is visibly ignored. Importantly, the problems of the Untouchables were discussed in the national political spectrum and the new Constitution offered them a new identity and special provisions
to facilitate their entry into mainstream civil life, the Hindi cinema of 1950s neglected their concerns and voices under the influence of nationalistsocialist rhetoric. It is only in the neo-liberal era that the cinema industry witnessed the arrival of nuanced Dalit representation on screen.
Evaluation of Baby Sleep Position Practices and Sleep Environment
Authors: ÇATAKLI Tülin , ŞENEL Saliha
Published: January 2023

Objective: The aim of this current study was to determine mothers’ infant sleep position practices and their awareness of a safe sleeping environment.
Material and Methods: This descriptive survey was conducted with 418 mothers who had infants aged 0-6 months and who agreed to participate in pediatric outpatient polyclinics of two hospitals. Data were collected between January-December 2020 via-structured questionnaires by face-to-face interview.
Results: Of the 418 mothers; 28% placed their babies in the supine sleeping position, 59.6% used a pillow when they put their babies in bed and 76.8% used a soft mattress. 42.3% of mothers covered their babies’ faces during sleep; primary school graduate mothers were more intended on covering their babies’ faces than high school and university graduates (p<0.001). 4.1% of mothers smoked during pregnancy, 9.8% during the lactation period and 15.3% were exposed to household smoke. All of the mothers shared a room with their babies without sharing a bed. There was also a positive correlation between the number of prenatal visits of mothers and their preference to put their babies to sleep in the supine position (p=0.010).
Conclusion: Most of the mothers placed their babies in a side sleeping position. Mothers’ avoiding sharing beds and smoking cigarettes and prone positioning their children at a very low frequency were pleasing measures. Mothers who had more prenatal visits were found to place their babies more in the supine sleep position. Increasing the awareness of healthcare providers and other secondary caregivers about a safe sleeping environment and baby sleep position during pre and postnatal visits would make right practices become widespread.
Laying the Tracks for Hydrail
Authors: Westbroek Wido
Published: January 2023

Hydrogen fuel cell rail systems are gathering steam, according to Cummins, which has recently broken ground on a new production facility to support Alstom with its plans to deploy hundreds of hydrogen trains over the next few years
Milling About
Authors: Kozica Elvis
Published: January 2023

The world´s first hydrogen-powered rail milling machine will be put into service by the end of 2021, offering an clean option for track maintenance and promising significant cost savings
Power Up
Authors: Bächli Jennifer
Published: January 2023

Bächli’s head of R&D Frank Hanisch reveals how the Smart-E-Power range is helping reduce electrical losses and save costs
Three Decades of Road and Trail Runoff and Erosion Work in the Northeastern Caribbean – a Research Program Perspective
Authors: Ramos Scharron Carlos E. , Alicea Efrain E. , Figueroa Sanchez Yasiel , LaFevor Matthew C. , McLaughlin Preston , MacDonald Lee H. , Reale-Munroe Kynoch , Thomaz Edivaldo L. , Viqueira Rios Roberto
Published: January 2023

Highlights

The infiltration capacities of unsurfaced roadways are frequently exceeded by rain intensity, promoting overland flow.

Erosion rates from unsurfaced roadways and cut slopes are 101 to 104 times greater than on undisturbed hillslopes.

Roads in steep, subtropical wet terranes may increase landslide erosion by a factor of 5 relative to areas without roads.

The hydro-geomorphic impact of roads is so prominent that they must be explicitly considered in watershed assessments.

ABSTRACT. Erosion is a key environmental concern in the northeastern Caribbean because it can diminish soil productivity, damage infrastructure, and threaten human life. Additionally, sediment released by erosion can be delivered to streams where it can degrade water quality and aquatic habitat, reduce reservoir storage capacity, and threaten critical marine resources such as sea grass beds and coral reefs. Road erosion has been a concern in the region since the 1990s, and a considerable body of research has been conducted over the last ~30 years. This article reviews the key findings and identifies additional research needs. In some tropical dry coastal watersheds of the US Virgin Islands and Puerto Rico, unpaved roads and foot or off-road vehicle trails are the primary sediment sources. Watershed scale sediment production rates in these tropical dry settings are 0.3 to 3.7 Mg ha-1 yr-1, depending on unpaved road density, and these are 3 to 40 times greater than under undisturbed conditions. In wetter settings, like the forested and actively cultivated landscapes of highland Puerto Rico, sediment contributions include those from unpaved farm roads but also those from croplands, streambanks, and landslides. Watershed scale sediment production rates in actively cultivated tropical wet settings are 15 to 60 Mg ha-1 yr-1, with road-induced surface erosion and landslides accounting for 50% to 95% of total sediment production. Designing management alternatives will require additional research to improve our understanding of road-to-stream and road-to-coast connectivity, develop effectiveness metrics of applied management practices, and establish the specific causes of road-induced landslides. Keywords: Connectivity, Coral reefs, Landslides, Puerto Rico, Sedimentation, Surface erosion, Virgin Islands.
Tecendo as relações naturais
Authors: De Lucena Costa Isabel Maria
Published: January 2023

Mandala realizada com a tecnica de desenho a mão livre. Utilizando lápis de cor aguarelado.
SCCP
Authors: Santos Carlos Roberto
Published: January 2023

O controle religioso do Estado sobre o sexo moldando uma população extremamente conservadora e submissa.
Amanhecendo em Lençois
Authors: De Britto Rogério Grillo
Published: January 2023

O amanhecer na cidade de Lençois, lindíssimo.
Costureira de sonhos
Authors: Oliveira Ana Silva
Published: January 2023

Poesia a ser submetida para a Revista Pai Inácio de Literatura e Arte.
Remador
Authors: Remanso Maya
Published: January 2023

Título: RemadorDimensão: 15cm x 20.5cm Técnica: tinta óleo no quadro.Descrição: A maioria das pessoas são acostumados de andar de barco no Rio Marimbus, seja pescando, passiando, ou levando turistas para o Roncador.
Policy analysis and regional governments
Authors: Noferini Andrea , Sancho David
Published: January 2023

As democratically elected institutions responsible for nearly half of total public expenditure, Spanish regional governments participate in the policy analysis process and generate their own information and technical knowledge about policy problems. In this chapter, we focus on Spanish regional governments as policy analysts in a context of increasing state intervention, greater decentralization and growing policy complexity. The chapter analyses this greater demand for policy analysis at the regional level in the light of the territorial distribution of powers between the center and the periphery; the historical and administrative legacy of the Spanish administrative system; the role of regional government in some basic policy areas of welfare, and the localization of the 2030 Agenda in two regions: Catalonia and the Basque Countries.
NGOs as policy analysis partners: from invisibility to expansion
Authors: Márquez Luz , Guerrero Noemí Orué
Published: January 2023

In Western countries NGOs have had little involvement in the formulation of public policies, and their intervention has been more consultative in nature. This has been the case especially in the Spain. Though during the last three decades Spanish NGOs have been included as policy advisors in governmenta and parliamentary venues, increassing the possibility to translate their policy expertise and knowledge. In this chapter, we explain the evolution of this trend and we present evidence of their role as policy analysis partners in Spanish politics. We show that notwithstanding their consolidation in general terms, few have access to funds or economic resources, either private or public, lack their capacity to develop policy analysis. A small group of NGOs concentrate economic resources and therefore have a greater capacity to recruit staff dedicated to policy analysis. In essence, this club of rich and big NGOs allocate continuous and daily resources to develop information for public policy analysis. While, the vast majority, for the most part small NGOs, do not have specialized internal advocacy or reporting units for policy analysis purposes.
Contemporary Challenges: Views From Local Authorities And ‘The Field’
Authors: Baginsky Mary , Driscoll Jenny , Purcell Carl , Manthorpe Jill , Hickman Ben
Published: January 2023

This chapter is based on the views of 68 professionals working in children’s social care or education services in England and an additional 26 interviews with people working in regional and national agencies involved in different aspects of safeguarding and education policy. These interviews contributed to a much better understanding of how schools and other agencies were responding to the concerns identified in our historical analysis in Chapter 2, as well as identifying the new challenges with which they were grappling. They also commented on the impact of the policies of academisation and austerity on local authorities, including their concerns that schools were losing the staff that support children’s welfare or were redeploying them to other areas of school life. They also reflect on the increasing expectations of schools and the changing nature of the problems that face them including poor parental and child mental health, radicalisation, social media, domestic violence and alcohol and substance abuse.