bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 1/2 randomized, open-label, multicenter, Simon two-stage study of pelareorep combined with modified FOLFIRINOX +/- atezolizumab in patients with metastatic pancreatic ductal adenocarcinoma.
Authors: Arnold Dirk , Loghmani Houra , Cheetham Karol , Trauger Richard , Heineman Thomas Charles
Published: July 2024

TPS4203

Background: Immune therapies benefit only the small subset of metastatic pancreatic ductal adenocarcinoma (mPDAC) patients who have microsatellite instability-high (MSI-H) tumors (approximately 1%). Most PDAC tumors are microsatellite stable (MSS) and have an immunologically “cold” phenotype with fewer genetic mutations, reduced immune cell infiltration, and downregulated immune checkpoint proteins. These attributes make most mPDAC tumors resistant to conventional immunotherapy including checkpoint inhibitors. Pelareorep is a naturally occurring, non-genetically modified reovirus that selectively infects cancer cells following intravenous administration. Upon infection, pelareorep’s double-stranded RNA genome stimulates a pro-inflammatory response that primes tumors for immunologic killing. This includes increased T cell infiltration into tumors, expansion of tumor-infiltrating lymphocyte clones, increased PD-L1 expression, and stimulation of tumor-directed innate and adaptive immune responses. Pelareorep combined with chemotherapy, checkpoint inhibitors, or both has shown promising efficacy in several malignancies, including mPDAC. This study is designed to evaluate pelareorep plus modified FOLFIRINOX with or without the PD-L1 inhibitor atezolizumab as first-line therapy in patients with mPDAC. Methods: This trial represents a new cohort within the ongoing GOBLET signal finding platform study in gastrointestinal cancers. This is a phase 1/2 randomized, open-label study that uses a screened selection design within a Simon two-stage approach. Eligible patients must be 18 years or older and have newly diagnosed, radiologically evaluable mPDAC with no prior chemotherapy and an ECOG performance status of 0 or 1. Patients are randomized 1:1 to receive either pelareorep + mFOLFIRINOX orpelareorep + mFOLFIRINOX + atezolizumab. The first stage enrolls 15 evaluable patients into each arm. If pre-specified efficacy criteria are met in Stage 1, one or both arms may be expanded to Stage 2 and enroll 17 additional evaluable patients per arm. The first 3-6 patients enrolled into both arms comprise a safety run-in that must be successfully concluded prior to enrolling additional patients. The treatment period consists of 4-week treatment cycles. The primary objectives are 1) safety and tolerability of pelareorep + mFOLFIRINOX with or without atezolizumab and 2) efficacy based on objective response rate per RECIST v1.1. Secondary objectives include duration of response, progression-free survival, and overall survival. In addition, tumor and blood samples are being collected to evaluate the immunological effects of treatment and to explore potential biomarkers of response. Clinical trial information: Eudra-CT: 2020-003996-16.
Targeting replication stress in pancreatic cancer: A phase II trial investigating azenosertib in combination with gemcitabine in second-line advanced pancreatic cancer.
Authors: Huffman Brandon , Horick Nora K. , Bird Alexandra , Gibson Caroline , Brais Lauren K. , Graham Christopher , Schlechter Benjamin L. , Wolpin Brian M. , Aguirre Andrew , D'Andrea Alan D. , Shapiro Geoffrey Ira , Cleary James M.
Published: July 2024

TPS4211

Background: A major unmet need in pancreatic cancer (PDAC) is molecularly targeted treatment options for patients who develop resistance to first-line platinum chemotherapy. While combined gemcitabine and nab-paclitaxel is commonly used after progression with first-line therapy, the efficacy in the second-line setting is fair, with recent phase clinical trial data demonstrating a median progression-free survival (PFS) of 2.7 months and a median overall survival of 6.6 months (1). In recent years, preclinical work has identified that replication stress is a potential PDAC vulnerability. The WEE1 kinase regulates the checkpoint governing the G2/M transition of the cell cycle to compensate for replication stress. The G2/M checkpoint is critically important in malignancies like PDAC where over 75% of tumors have p53 pathway deficits. Therapies that inhibit cancer cells’ ability to compensate for replication stress are particularly attractive in cancers that have genomic alterations that generate replication stress. It has been demonstrated that in vitro and in vivo PDAC models were exquisitely sensitive to WEE1 inhibition in combination with gemcitabine. Azenosertib (Zn-c3) is an orally available, highly selective, nanomolar inhibitor of the WEE1 kinase and when combined with gemcitabine in PDAC cell lines, synergistic cytotoxicity is observed. Methods: NCT06015659 is an ongoing phase II clinical trial with safety lead-in that is testing the azenosertib WEE1 inhibitor combined with gemcitabine in patients with advanced pancreatic cancer after progression or intolerance with FOLFIRINOX. Subjects are dosed once daily, days 1-5, 8-12, and 15-19 with azenosertib and receive gemcitabine 800 mg/m2 on days 1 and 8 of 21-day cycles. Up to 12 subjects are expected to enroll in the safety lead-in portion based on a typical 3 + 3 design. Once the recommended phase 2 dose is confirmed, we will use a Simon two-stage minimax design to evaluate efficacy where the null hypothesis is that the true 6-month PFS rate is ≤ 24% (unacceptable historical control data) and the alternative hypothesis is that the true 6-month PFS is ≥ 44%. Pretreatment and on-treatment tumor biopsies are incorporated into the trial to identify potential biomarkers of treatment response. Subjects must be able to swallow oral tablets and have measurable disease by RECIST v1.1; prior exposure to gemcitabine is not allowed. Enrollment began November 21, 2023, and is ongoing. 1. Huffman BM, Basu Mallick A, Horick NK, et al. JAMA Netw Open. 2023;6(1):e2249720. Clinical trial information: NCT06015659 .
A randomized, multicenter, open-label phase III trial of hyperthermic intraperitoneal chemotherapy in platinum-resistant recurrent ovarian cancer (KOV-HIPEC-02).
Authors: Lim Myong Cheol , Kim Ji Hyun , Park Eun Young , Jeong Dae Hoon , Lee Yoo-Young , Choi Chel Hun , Lee Sungjong , Lee Shin-Wha , Park Jeong-Yeol , Kim Se Ik , Baek Jong Chul , Ha Hyeong In , Song Yong Jung , Jeon Seob , Lee Taek Sang , Jeon Hye won , Kim Ki Hyung , Park Sang-Yoon
Published: July 2024

TPS5635

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery has emerged to achieve a higher concentration of chemotherapeutic agents and treat micro-metastases on peritoneal surfaces. At advanced staged ovarian cancer treated with neoadjuvant chemotherapy, HIPEC during interval cytoreductive surgery with cisplatin 75-100mg/m2 increases progression-free survival and overall survival (OV-HIPEC-01 and KOV-HIPEC-01). In chemotherapy-naïve ovarian cancer patients, survival benefit is not identified with HIPEC (KOV-HIPEC-01). And the meta-analysis revealed the survival benefit after recent exposure of chemotherapy. In ovarian cancer, HIPEC is thought to overcome chemotherapy resistance. Methods: This trial (KOV-02) is currently actively enrolling, a multicenter, open-label, 1:1 randomized, phase III trial that will enroll 140 patients in platinum-resistant recurrent epithelial ovarian cancer. The trial is registered on ClinicalTrials.gov (NCT05316181). Institutional review board approval was obtained. The first patient was enrolled on April 07, 2022. The experimental arm will receive cytoreductive surgery and HIPEC (Doxorubicin 35mg/m2 and mitomycin 15mg/m2, 41.5-42.0°C) followed by physician-choice chemotherapy, and the control arm will receive physician-choice chemotherapy until disease progression or intolerable toxicity. The primary objective of the trial is to evaluate progression-free survival (PFS) between the HIPEC group and the control group. Secondary objectives are overall survival (OS), cancer-specific survival, safety, and quality of life. Assuming that the enrollment period is three years and the follow-up period is two years, the total number of events required is 121. Based on the log-rank test, the total number of subjects required to prove HR 0.6 with a two-sided alpha of 0.05 and 80% power is 126. Considering 10% drop-out, 140 patients are finally studied. Clinical trial information: NCT05316181 .
Rationale and study design of the KOV-HIPEC-04: A phase III randomized controlled trial in primary stage III and IV ovarian cancer after interval cytoreductive surgery (FOCUS).
Authors: Lim Myong Cheol , Kim Ji Hyun , Park Boram , Lee Jung-Yun , Chang Suk-Joon , Lee Yoo-Young , Choi Chel Hun , Park Jeong-Yeol , Kim Dae-Yeon , Hong Dae Gy , Cho Hyun-Woong , Song Jae-Yun , Kim Yun Hwan , Kim Ki Hyung , Park Sang-Yoon , You Benoit , Jeon Seob
Published: July 2024

TPS5636

Background: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery increases progression-free and overall survival for patients with stage III ovarian cancer in two randomized controlled trials (OV-HIPEC-01 and KOV-HIPEC-01) in the era of platinum. The aim of this trial is to identify the survival benefit of HIPEC in stage III & IV ovarian cancer with maintenance therapy of bevacizumab and/or PARP inhibitor. Methods: The KOV-HIPEC-04 trial is the international, multicenter, 1:1 randomized, phase III trial that will enroll 520 patients with stage III & IV ovarian cancer who received neoadjuvant chemotherapy. Patients with residual tumor < 2.5mm after interval cytoreductive surgery will be randomized to the trial arm (HIPEC, 41.0-42.0°C cisplatin 75mg/m2, 90 minutes) or control arm. After recovery from surgery, patients will receive postoperative platinum-based adjuvant chemotherapy followed by maintenance therapy with PARP inhibitor or bevacizumab by the institutional guideline based on BRCA/HRD status. The primary endpoint is to evaluate overall survival (OS); secondary objectives are progression-free survival (PFS), cancer-specific survival, time to the first subsequent therapy, safety, and quality of life. Assuming that the enrollment period is 5 years and the follow-up period is 3 years, the total number of events required is 263. Based on the log-rank test, the total number of subjects required to prove HR 0.67 with a two-sided alpha of 0.05 and 90% power is 494. Considering 5% drop-out, 520 patients are finally enrolled. ClinicalTrials.gov (NCT05827523). Clinical trial information: NCT05827523 .
GOG 3088: A randomized phase II study of letrozole versus observation in patients with newly diagnosed uterine leiomyosarcoma.
Authors: Corr Bradley , Sill Michael , Klein Jennifer , Herzog Thomas J. , Coleman Robert L. , Slomovitz Brian M.
Published: July 2024

TPS5643

Background: Uterine leiomyosarcomas (uLMS) are rare, accounting for less than five percent of all malignant uterine neoplasms. Approximately 85% of women present with clinical stage I disease (i.e., disease limited to the uterus and cervix). NCCN guidelines for stage I uterine confined disease currently recommend observation; however, recurrence risk of uLMS overall is quite high at 50-70% within the first two years. The estrogen receptor (ER) is expressed in 40-87% of leiomyosarcomas. Because of this high expression, estrogen may act as a growth factor that stimulates cell proliferation and tumor growth. Subsequently, there have been several evaluations for the use of aromatase inhibitors as single agent therapy for uLMS. These trials have each shown varying degrees of clinical activity. We hypothesize that by decreasing systemic estrogen using an aromatase inhibitor we will prolong the time to recurrence for patients with this disease. Methods: This is a GOG Foundation led phase II randomized controlled trial comparing letrozole (2.5mg PO daily) to observation in newly diagnosed patients with uterine confined stage I uLMS. Forty patients will be randomized 1:1. Patients will be eligible post operatively if they have no measurable disease and will be required to be estrogen receptor (ER) positive, as defined by ³ 10% expression by immunohistochemistry (IHC). No stratification methods will be applied. The primary endpoint of the trial is investigator-assessed progression free survival. Exploratory translational evaluation will occur to 1) correlate response to letrozole based on IHC hormone receptor status, 2) evaluate gene expression signatures of hormone receptor activity, tumor biology, and tumor microenvironment in relation to response to letrozole, and 3) evaluate the contribution of single nucleotide polymorphism rs3820282 to tumor biology and response to letrozole. GOG 3088 activated in January of 2024 and expects to enroll across 20 US sites. Clinicaltrials.gov Identifier: NCT05649956. Clinical trial information: NCT05649956 .
Phase II trial assessing safety, efficacy and immune correlates of heterologous prime-boost with pBI-11 (IM) and TA-HPV (IM) plus pembrolizumab for advanced, PD-L1 CPS≥1, hrHPV+ oropharyngeal cancer.
Authors: Gibson Michael K. , Roden Richard , Wu TC , Heimann-Nichols Ellen
Published: July 2024

TPS6118

Background: HPV-related OPSCC occurs in younger patients, has a significantly better prognosis, and is most often caused by HPV subtype 16. There is a 90% overall survival for HPV+/p16+ OPSCC (40% for HPV-/p16- OPSCC), which can be cured with multimodality care. For patients with R/M disease, treatment with pembrolizumab (P) +/- chemotherapy is palliative, with a median OS of approximately 12 months for patients with PD-L1 combined positive score (cps) >1 treated with P alone. Heterologous prime boost with DNA priming followed by vaccinia-based boosting against HPV16 viral antigens will be studied using pBI-11 [(DNA vaccine pNGVL4a-SigE7 (detox)/HSP70, HPV16 E7(detox)/ HPV18 E7(detox), HPV16 E6(detox), and HPV18 E6(detox)] followed by TA-HPV (recombinant vaccinia-human papillomavirus (denoted TA-HPV) derived from the Wyeth strain of vaccinia which carries modified E6 and E7 genes from HPV types 16 and 18). This study is approved by the Vanderbilt University IRB and is open accrual (NCT NCT05799144). Methods: Patients with R/M, HPV positive OPSCC without prior therapy for R/M disease, without contraindications to immunotherapy and with a PD-L1 cps > 1 will be screened. There is a 6 patient safety run-in. Treatment with pBI-11 vaccine (2 IM injections on weeks 1 and 4) plus one IM administration of TA-HPV on week 7 will be given in combination with P IV on weeks 1, 4, and 7). Following restaging, all patients will continue (including those with PD) with 3 more cycles of P followed by restaging. The primary clinical outcome is RR to addition of vaccine in the 50% of predicted P non-responders (NR) who proceed to Part II (ie conversion to responders). All responders will continue to receive P until progression. Approximately 54 patients with be enrolled. Two research tumor biopsies and blood draws will be obtained pre- and on treatment (week7-9). Tumor tissue cores will be utilized for immunohistochemical and molecular tests (e.g., expression of immune cell and viral markers, TCR sequencing and total transcripts). Blood with be tested for HPV16/18 E6, E7 antibodies and vaccinia virus neutralizing assays; proliferative responses of peripheral blood lymphocytes to stimulation by HPV16/18 E6 and E7; HPV16/18 E6- and E7-Specific T cells; and HPV DNA in plasma. Data from the 1st four patients enrolled will be presented. Clinical trial information: NCT05799144 .
Characterization of Turner Syndrome-associated Diabetes Mellitus
Authors: Cameron-Pimblett Antoinette , La Rosa Clementina , Davies Melanie C , Suntharalingham Jenifer P , Ishida Miho , Achermann John C , Conway Gerard S
Published: July 2024

Context

Diabetes mellitus (DM) risk factors in Turner syndrome (TS) may include autoimmunity, obesity, β-cell dysfunction, genetic predisposition, and insulin resistance (IR).

Objective

This work aimed to evaluate glucose tolerance and DM risk factors in adults with TS.

Methods

A single-center study with 2 phases was conducted to determine the prevalence of DM and to assess DM risk markers comparing women with TS with and without impaired glucose tolerance (IGT). The study took place at a tertiary referral center, University College Hospitals. A total of 106 women with TS (age range, 18-70 years) undergoing annual health surveillance underwent oral glucose tolerance tests (OGTTs), with additional samples for autoimmunity and genetic analysis. Main outcome measures included glucose tolerance, insulin, autoimmune, and single-nucleotide variation (SNV) profile.

Results

OGTT screening showed that among those without a previous DM diagnosis, 72.7% had normal glucose tolerance, 19.5% had IGT, and 7.6% were newly diagnosed with DM. OGTT identified more cases of DM than glycated hemoglobin A1c sampling alone. Women with IGT or DM were older, with higher body mass index and IR. No association was found between autoimmune markers glutamic acid decarboxylase (GAD), islet antigen-2, and zinc transporter 8, risk karyotypes, or selected SNVs and DM. In DM cases, GAD positivity was associated with requirement for insulin therapy. The median age of onset of the diagnosis of DM was 36 years (range, 11-56 years).

Conclusion

In the spectrum of DM subtypes, TS-associated DM lies between type 1 and type 2 DM with features of both. Key factors include weight and IR. Assessing C-peptide or GAD antibodies may aid future insulin requirement.
Structure and sequence at an RNA template 5′ end influence insertion of transgenes by an R2 retrotransposon protein
Authors: Palm Sarah M. , Horton Connor A. , Zhang Xiaozhu , Collins Kathleen
Published: July 2024

R2 non-long terminal repeat retrotransposons insert site-specifically into ribosomal RNA genes (rDNA) in a broad range of multicellular eukaryotes. R2-encoded proteins can be leveraged to mediate transgene insertion at 28S rDNA loci in cultured human cells. This strategy,preciseRNA-mediatedinsertion oftransgenes (PRINT), relies on the codelivery of an mRNA encoding R2 protein and an RNA template encoding a transgene cassette of choice. Here, we demonstrate that the PRINT RNA template 5′ module, which as a complementary DNA 3′ end will generate the transgene 5′ junction with rDNA, influences the efficiency and mechanism of gene insertion. Iterative design and testing identified optimal 5′ modules consisting of a hepatitis delta virus–like ribozyme fold with high thermodynamic stability, suggesting that RNA template degradation from its 5′ end may limit transgene insertion efficiency. We also demonstrate that transgene 5′ junction formation can be either precise, formed by annealing the 3′ end of first-strand complementary DNA with the upstream target site, or imprecise, by end-joining, but this difference in junction formation mechanism is not a major determinant of insertion efficiency. Sequence characterization of imprecise end-joining events indicates surprisingly minimal reliance on microhomology. Our findings expand the current understanding of the role of R2 retrotransposon transcript sequence and structure, and especially the 5′ ribozyme fold, for retrotransposon mobility and RNA-templated gene synthesis in cells.
Two Byzantine Medical Texts in Verse Translated into English: Diagnosis and Treatment of Disease
Authors: Bouras-Vallianatos Petros
Published: July 2024

This article aims to provide an English translation of two particularly popular Byzantine medical texts in verse, focusing on diagnosis by the examination of venesected blood and urine. Furthermore, these texts provide valuable therapeutic advice, especially for the use of drugs. They are composed in the form of liturgical hymns, combining mnemonic techniques. These hymns survive in various recensions and are often ascribed either to Nikephoros Blemmydes or Maximos Planoudes, both late Byzantine intellectuals and renowned teachers of advanced educational programs in Nicaea and Constantinople, respectively.
The teaching of the Art and Science of Medicine
Authors: Cokkinos Dennis V.
Published: July 2024

Teaching of medicine hails back to the age of Hippocrates; in the “Oath” he considers his teachers equal to his parents. Teaching, clinical practice and research constitute the three pillars of medicine, and they are interconnected. The methods of teaching medicine are very important. Auditorium lectures are being replaced by teaching in small groups and problem-oriented teaching. Still the enthusiasm of the teacher who can also become a mentor is a critical ingredient. The teacher should not just transmit but also create knowledge. The advent of artificial intelligence provides new auxiliary tools but also poses new challenges. We must not forget that we are shaping the future of tomorrow.
Innovations in daily commuting - what types of solutions are competitive? European case study.
Authors: Wolny - Kucińska Ada , Dudzińska Małgorzata , Dawidowicz Agnieszka , Gross Marta
Published: July 2024

Innovations drive dynamic changes in daily commuting especially in functional urban areas (FUAs), where transport systems are developed. Innovative solutions are being tested in FUAs, and they not only pose an alternative to conventional transport systems, but can also revolutionize daily commuting in cities. The main aim was to classify the innovation drivers identified in literature and to determine their impact on travel behaviour (TB) in FUAs with a use of expert survey. The following research hypothesis was examined: the level of innovation utilization in daily commuting and its impact on TB is similar in countries with similar levels of economic development. The survey results were processed to (1) create a ranking of innovations in TB in European OECD countries and (2) group countries based on similarity in prioritizing innovations influencing TB, using Ward hierarchical clustering method. As a result, innovative factors were comprehensively identified and classified in six categories.
Kwestia narodowościowa w optyce polskiej i rosyjskiej emigracji na przełomie lat czterdziestych i pięćdziesiątych XX w.
Authors: Dryblak Łukasz
Published: July 2024

Kwestia narodowościowa w Związku Sowieckim była jedną z ważniejszych osi dyskusji prowadzonych przez polską i rosyjską emigrację. Stosunek do narodów prometejskich, przez Rosjan określanych separatystycznymi, był kluczowy dla koncepcji politycznych promowanych przez polskie i rosyjskie ośrodki emigracyjne. W swoim artykule dowodzę, że dominująca w polskiej polityce postawa antyimperialna i coraz szersze po wojnie poparcie dla niepodległości Ukrainy miały wpływ na myślenie rosyjskich demokratów. Rosjanie zmuszeni byli do modyfikacji swoich programów politycznych, także ze względu na okoliczności międzynarodowe.
The Nobility of the Kaunas District in the Local Sejmiks of 1615 and 1632
Authors: Jaramičius Ričardas
Published: July 2024

Based on the instructions of the Kaunas sejmiks of 1615 and 1632, the article analyses the questions resolved by the nobility of the Kaunas district related to the life of the district and the whole Polish-Lithuanian Commonwealth. A particular focus is given to how different state processes and events were reflected in the sejmiks of the Kaunas district. The article also includes a list of nobility who signed the 1615 sejmik instructions.
Diakonische Pastoral – Leitungsmodelle und synodale Entwicklungen
Authors: Kießig Sebastian , Celary Ireneusz
Published: July 2024

Die diakonische Pastoral ist fortwährend präsent, sichtbar und Gegenstand vielfacher kirchlicher Reflexionen. Weihepriesterliche Leitungen waren in der historischen verbandlichen Caritas sichtbare Tradition, in der gegenwärtigen Zeit ist diese rückläufig und zugleich theologisch nicht notwendig. Auffällig ist, dass der pastoralen Umgestaltung einer diakonischen Pastoral wie einer Pastoral in der (verbandlichen) Caritas neue Priorität eingeräumt und diese als gestärkt angesehen werden.
Diese Befunde aus dem Engagementbereich der (verbandlichen) Caritas zeigen, dass eine diakonische Pastoral sich weiterhin fluide verändert und zugleich positives Gestaltungspotential für die Kirche entwickelt. Insbesondere die Dimension von Synodalität bieten Chancen, auch eine verbandliche Caritas in ihrer praktischen Leitung mit dem Stil kirchlichen Führens (und damit ihres Sendungsauftrages) zu kombinieren.
How Framing Influences Strategic Interactions
Authors: Hsee Christopher K. , Imas Alex , Li Xilin
Published: July 2024

In many settings, a person’s outcome depends not only on her own behavior, but also on her counterpart’s. Such strategic decisions have traditionally been studied using normative game theory, which assumes that people adopt equilibrium strategies and will reach the same decision, regardless of how the problem is described (framed). We examine a potentially important type of framing effect—focusing on how the relationship between players’ actions generates joint outcomes. Any strategic interaction can be described by either spelling out the outcomes of all possible action combinations (which we call “outcome framing,” or simply “O-framing”) or describing what will happen if different players choose the same action or choose different actions (which we call “relation framing,” or simply “R-framing”). O-framing has been the typical way to describe a strategic problem in prior work, whereas R-framing is commonly employed in real-life communications. We propose that these functionally equivalent frames induce different psychological processes and lead to different decisions: Relative to O-framing, R-framing increases players’ beliefs about their counterparts’ likelihood of coordinating on a cooperative option. We demonstrate this effect in the context of classic games such as the Prisoner’s Dilemma and the Stag Hunt. We find that, compared with O-framing, R-framing significantly increases people’s likelihood to choose the action that maximizes collective benefits rather than individual interests, and it does so by increasing beliefs that one’s partner will choose the same action as well. We derive conditions when this effect is likely to emerge and discuss the managerial implications of this research.

This paper was accepted by Yuval Rottenstreich, behavioral economics and decision analysis.

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.00518 .
Establishing Geographical Indicator of Fermented Cacao Beans Using Microbiome Fingerprinting
Authors: Nugroho Imam Bagus , Siregar Abdul Rahman
Published: July 2024

Geographical indication is an essential label for industrial products. Herein, we aimed to explore a method for establishing geographical indications based on microbial diversity data. We collected two groups of datasets available on the public server of the European Nucleotide Archive. These datasets contain 12 (twelve) NGS-generated reads (amplicon sequencing metagenomes) of fermented cacao beans from Brazil and Mexico. We extracted the microbiome profile using bioinformatic tools in the SHAMAN server. We analyzed further using Principal Component Analysis, Clustering (Ward’s Method of Hierarchical Agglomerative Clustering), and UMAP (Uniform Manifold Approximation and Projection) combined with KNN (K-Nearest Neighbor). We discovered differences in microbial diversity and unique taxa in the fermented cacao beans from Brazil and Mexico. Lactic acid bacteria (LAB), such as Liquorilactobacillus, Tatumella, Leuconostoc, Companilactobacillus, and Limosilactobacillus, are unique genera in samples from Mexico, while Bacillus is a unique genus found in samples from Brazil.  We have demonstrated the separation of the microbiome profiles between fermented cacao beans from Brazil and Mexico using PCA, clustering analysis and UMAP-KNN. We have successfully developed the proof of concept in establishing geographical indicators based on microbial diversity data or microbiome profiles. In the future, we will extend this research to analyze samples from Indonesia and establish a microbial diversity database of Indonesian fermented cacao. This database is essential for the authentication assay of Indonesian fermented cacao and for developing fine cacao and specialty products.
Perencanaan Strategik Sarana Prasarana di SMA Al Falah Ketintang Surabaya
Authors: Rosyidi Muhammad , Veroniva Junia Thre , Jariyah Ainun , Aj-Jaudah Salsabila , Ghorizah Fithrotul , Wulandari Ayu , Nuphanudin Nuphanudin
Published: July 2024

Penelitian ini yang berjudul "Perencanaan Strategik Sarana dan Prasarana di SMA AL Falah Ketintang Surabaya", bermaksud  untuk fasilitas yang ada dapat memenuhi kebutuhan penggunaannya secara efektif dan efisien. Hal tersebut terlihat dari adanya sarana prasarana yang cukup memadai, serta menyesuaikan kebutuhan peseta didik pada SMA Al Falah Ketintang Surabaya. Sarana dan prasarana tersebut dikelola secara langsung oleh para pendidik maupun staf karyawan bidang tugas masing-masing seperti bidang kebersihan dan pemeriksaan sarana prasarana seperti : pemeriksaan kendala AC setiap 3 bulan sekali, kebersihan toilet serta fasilitas umum lainnya yang di lakukan setiap hari, dibawah pengawasan Waka sarana dan prasarana, langkah tersebut dimaksudkan untuk meningkatkan efektivitas, efisien serta menciptakan kenyamanan proses pembelajaran. Kemudian pengelolaan fasilitas dan infrastruktur dilakukan sebagai bagian dari proses manajemen. Selanjutnya, pelaksanaan manajemen fasilitas dan infrastruktur pendidikan, SMA Al Falah Ketintang Surabaya dilaksanakan secara bersinambung, berawal dari perencanaan pengadaan,  pemeliharaan, pencatatan inventarisasi hingga proses penghapusan. Prosedur tersebut di laksanakan agar manajemen sarana dan prasarana yang di lakukan selalu berada dalam keadaan ketertiban dan keteraturan sesuai dengan tujuan yang sudah di rencanakan. Metode penelitian yang digunakan dalam, artikel ini yaitu menggunakan metode kualitatif. Adapun metode pengumpulan data dilakukan dengan metode wawancara dan observasi. Penulis merekomendasikan untuk pihak sekolah dapat memenuhi berbagai sarana prasarana serta fasilitas yang dibutuhkan oleh siswa lebih banyak dan lengkap lagi seperti pembagian alat kebersihan disetiap kelasnya. menambahkan pemasangan Wi-Fi atau menambah kecepatan Wi-Fi, serta apabila ada kerusakan pihak sekolah diharapkan memperhatikan sarana apa yang sekiranya perlu diganti maupun diperbaiki untuk kenyamanan  pengguna fasilitas sekolah.
Pengembangan Media Smart Box Literasi Untuk Meningkatkan Kemampuan Membaca Permulaan Pada Siswa Kelas Ii SDN Inpres Mangge Dalam Kec. Lambu
Authors: Komalasari Desy Ningsih , Hardiningsih Sri , Mulyadi Mulyadi , Wulandari Sri
Published: July 2024

Tujuan dari penelitian ini adalah untuk mengetahui (1) proses pengembangan media smart box literasi siswa kelas II di Sdn Inpres Mangge Dalam (2) hasil kelayakan produk pengembangan media smart box literasi pada siswa kelas II di SDN INPRES Mangge Dalam (3) keefektivan pembelajaran menggunakan media smart box literasi pada siswa kelas II di SDN INPRES Mangge Dalam. Penelitian ini merupakan penelitian pengembangan atau dikenal dengan R&D (Research ang Development) yang dilakukan menggunakan model penelitian 4D (Four D Model), meliputi tahap pendefenisian (define), perancangan (design), pengembangan (development), dan diseminasi (disseminate). Subjek Penelitan ini adalah siswa kelas II Sdn Inpres Mangge Dalam, dengan uji coba skala kecil 5 orang siswa bertujuan untuk melihat kepraktisan media smart box literasi dan uji coba skala besar dilakukan terhadap seluruh siswa kelas II sejumlah 12 orang bertujuan untuk mengukur efektivitas media smart box literasi dalam meningkatkan kemampuan membaca permulaan,keefektivan pembelajaran menggunakan media smart box literasi pada siswa kelas ii di Sdn Inpres Mangge dalam. Hasil validasi sangat baik yaitu, validasi media memperoleh skor 94,44% (sangat layak), artinya media yang didesain sudah dapat diaplikasikan setelah mendapatkan validasi dari validator, validator materi memperoleh skor 96% (sangat layak) karena materi yang digunakan pada media pembelajaran sangat relevan dengan kondisi peserta didik, dan validator praktisi lapangan memperoleh skor 92,5% (sangat layak) seorang praktisi memberikan tanggapan berkaitan dengan media dan materi yang digunakan sangat relevan dengan kondisi peserta didik maupun lingkungan sekolah. Uji coba skala kecil memperoleh 93,75% hasil yang didapat setelah menerapkan media mada materi pembelajaran yang sudah divalidasi oleh validtor dan hal tersebut sudah sangat layak digunakan dalam proses pembelajaran untuk meningkatkan kemampuan membeca permulaan peserta didik.
Outcome Measures for Sjögren Disease—Novel Developments and Further Needs
Authors: Wilson Robert , Townsend Jaiden , Hawkins Ellie , Ciurtin Coziana
Published: July 2024

Sjögren disease (SjD) is a systemic autoimmune disorder affecting both children and adults, with a wide range of clinical phenotypes. It remains a challenging condition to recognise and diagnose early and manage effectively. The heterogeneous nature of the presentation, variable disease course and overlapping symptoms with other autoimmune conditions often result in delayed diagnosis. This, coupled with the lack of licensed effective therapies frequently leads to suboptimal patient outcomes. Improved outcome measures are crucial for advancing our understanding of SjD pathogenesis and developing effective treatments. They can help ensure that clinical trials are accurately capturing the impact of potential therapies on the disease and the quality of life of people with SjD. Further developments are needed in the areas of age and developmentally appropriate disease and patient-reported outcome measures, with adequate sensitivity to evaluate treatment efficacy, as well as predictor biomarkers for both treatment response and poor prognostic outcomes associated with SjD. Advancing these areas will help ensure that clinical trials adequately select the most suitable SjD cohorts to treat with a certain therapy, as well as accurately reflect the impact of a certain intervention on disease activity, progression, and quality of life, ultimately leading to better care for people with SjD.
A Systematic Review and Meta-Analysis of Kiwifruit’s Impact on Functional Constipation
Authors: Cokro Fonny , Vashti Ervina , Nurcahyanti Agustina Dwi Retno , Sumarpo Anton , Malasao Rungnapa
Published: July 2024

Introduction: Kiwifruit is rich in nutrients and fibers that benefit the digestive system. Despite various clinical investigations on the efficacy of kiwifruit for constipation, conflicting results are present. Therefore, the purpose of this meta-analysis was to evaluate the effectiveness of kiwifruit in treating functional constipation. Methods: The study’s main goal is to quantify the frequency of defecation. Randomized-controlled trials (RCTs) were explored from four databases, including Cochrane Library, ProQuest, Science Direct, and MEDLINE, with Google Scholar as an additional database for hand-searching purposes. The Risk of Bias 2 (RoB2) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tools were employed to evaluate the certainty of evidence. The meta-analysis was carried out using RevMan. Results: After critically appraising the individual articles, the study includes five randomized controlled trials (RCTs). The results indicated that defecation frequency improved considerably, with a p-value of 0.0008 and a weighted mean difference (WMD) of 0.07. However, the GRADE analysis showed low-quality evidence. Conclusions: Kiwifruit may be a secure and efficient treatment for people with functional constipation. However, further high-quality clinical investigations are needed to confirm these results.
Phytochemical Analysis of Anthocyanins Extracted from the Flowers of Two Dahlia Cultivars and their Cytotoxic Properties
Authors: Gontova Tetiana , Mashtaler Viktoria , Romаnova Svitlana , Maloshtan Ludmila , Shanaida Mariia
Published: July 2024

Dahlia Cav. is a genus of ornamental plants that belongs to the Asteraceae family. These plants are visually pleasing and contain biologically active substances such as flavonoids, hydroxycinnamic acids, organic acids, and inulin. Among these substances, anthocyanins are especially noteworthy. These water-soluble vacuolar pigments of a glycoside nature have significant health benefits, including antioxidant, antidiabetic, hypocholesterolemic, anticancer, cardioprotective, and hypotensive properties. The purpose of this study was to evaluate the content of anthocyanins by spectrophotometry and the composition by HPLC in the extracts from flowers of two varieties of dahlias ('La Baron' and 'Colorado Classic') grown in Ukraine, as well as to evaluate the cytotoxic effect of these extracts. According to HPLC analysis, among 18 revealed anthocyanins the fower of ‘La Baron’ cultivar had the highest concentration of cyanidin-3-O-arabinoside (31.85%) and cyanidin-3-O-galactoside (23.01%) while ‘Colorado Classic’ accumulated more delphinidin-3-O-arabinoside (39.80%) and Delphinidin-3-O-galactoside (23.15%). Our study also found that malvidin, peonidin, and petunidin played a minor role in the coloration of the flowers. The total amount of anthocyanins was slightly higher in the flowers of the ‘La Baron’ cultivar (1.250%) compared to the ‘Colorado Classic’ one (1.138%). To determine the toxicity of anthocyanins, it was used an in vitro model of bone marrow cells (BMC) and found that the cytoprotective and cytotoxic activities of the anthocyanins were dose-dependent. Based on these findings, the study concluded that there is potential for developing new herbal medicinal products using dahlia flowers with a significant content of anthocyanins.
Review on Recent Development in Opioid Abuse-Deterrent Formulation Technologies and Regulatory Expectation
Authors: Darji Pravinkumar , Patel Jayendrakumar , Patel Binit , Parikh Shalin , Fnu Praneeth Ivan Joel , Nalla Seshadri
Published: July 2024

Chronic pain occurs as a result of several diseases and ailments. The problem of improper utilization of vital opioid medication has been a topic of substantial discourse during the last two decades, in conjunction with its application for the extended-term control of persistent pain. Abuse-deterrent formulations play a crucial role in comprehensive methods to manage the risks associated with opioids. These formulations diminish the allure and narcotic properties of opioids by restricting their capacity to be assimilated by the body. This diminishes the appeal and incentives for misusing altered opioid prescriptions, and also poses challenges in extracting the opioid substance for utilization in alternative manners. This article examines various regulatory measures, projected prerequisites for the licensing of abuse-deterrent formulations, and current activities aimed at producing opioid abuse-deterrent formulations as potential remedies to combat the opioid abuse pandemic. Considering the seriousness of the global opioid problem, it is crucial for various regulatory entities to come together to safeguard society from the opioid pandemic. This involves implementing a thorough policy on prescribing opioid medications to patients, conducting evaluations to determine the likelihood of addiction, and increasing efforts to approve only opioid drugs that are specifically tailored to prevent abuse.
UPLC-ESI-MS\MS Phytochemicals Profiling of n-Butanol Fraction of Xanthium strumarium Fruit Extract
Authors: Ezghayer Mohammed A. , Ahmed Omar Hussein , Tawfeeq Mostafa F.
Published: July 2024

The work aimed to explore the phytochemicals of various fractions of Xanthium strumarium fruit extract since this plant is found to be toxic for both humans and animals in Iraq. The extracts underwent phytochemical screening, which indicated the occurrence of flavonoids, alkaloids, phenols, coumarin, saponin, tannins, and terpenoids. After extraction, fractionation was done using hexane, chloroform, and N-butanol respectively, for identifying the phytochemicals found in each fraction, UPLC-electrospray ionization–tandem mass spectroscopy was used which revealed the presence of 6 sterol and terpenes compound in hexane fraction, Nine compounds were detected in the chloroform fraction, among which 2-acetyl-atractyligenin and Artemisinin were the primary components. Additionally, this particular plant has been found to contain these compounds for the first time. Furthermore, Pungiolide C, dihydroartemisinin, and atractylenolide II were also detected for the first time in this plant. For the n-Butanol fraction, eight diterpene glycosides were recognized, with Atractyloside and Carboxyatractyloside and their desulphated derivatives as the major compounds responsible for the plant's toxicity. The butanol fraction also showed the presence of eight phenolic compounds, among which caffeoylquinic acid derivatives and flavonoid Syringetin were the major compounds in this fraction.
Results of Chemical and Pharmacological Studies of the Mongolian Traditional Prescription "Arur-10"
Authors: Tsagaanbaatar Nyamdemberel , Dashzeveg Uranzaya , Nyamdemberel Nomindari , Urtnasan Myadagbadam , Chimedtseren Chimedragchaa
Published: July 2024

This study examines ARUR-10, the herbal prescription commonly utilized in Traditional Mongolian Medicine practices for the treatment of kidney disease and the improvement of physical strength. This investigation aims to establish a profile of the biologically active compounds, antioxidant activity, and the anti-inflammatory impact on the kidneys in the traditional ARUR-10 prescription. For this analysis, we used Thin-Layer Chromatography (TLC) to identify phenolic compounds in the traditional prescription. Quantification of these bioactive substances was determined by UV/Vis spectrophotometry. The traditional ARUR-10 prescription, or traditional drug, had a higher polyphenolic content of 12.9±0.361% (gallic acid equivalent) and a sum flavonoid content of 0.33±0.015% (Rutin equivalent). The antioxidant activity was measured using the inhibiting free radical’s DPPH method and evaluated using the IC50 value. The 100 μg/ml concentration inhibited free radicals by 68.47%, whereas 200 μg/ml inhibited them by 83.29%, with an IC50 of 92.4 μg/ml. This study concluded that the traditional ARUR-10 prescription contains many polyphenolic compounds and flavonoids and has antioxidant properties. ARUR-10 has a moderate level of toxicity and no signs of chronic toxicity have been detected. Urine excretion was 1.52 ± 1.23 times higher than in the distilled water group (0.97 ± 0.71). ARUR-10 at doses of 240 mg/kg (1.62±1.14) had a similar effectiveness to Hydrochlorothiazide (1.52±1.23). In the gentamicin-induced nephritis model, ARUR-10 reduced serum creatinine by 42.8%, uric acid by 14.9%, and urea by 32% at doses of 240 mg/kg, compared to the control group that produced the pathological model. It had a protective effect on the kidneys by preserving the tube structure; cell death and cell necrosis were not observed.
Time-resolved momentum microscopy with fs-XUV photons at high repetition rates with flexible energy and time resolution
Authors: Schiller Karl , Stupar Matija , Sternemann Lasse , Omar Alan , Saraceno Martin , Nitschke Jonah , Mischke Valentin , Janas David , Ponzoni Stefano , Zamborlini Giovanni , Saraceno Clara , Cinchetti Mirko
Published: July 2024

Time-resolved momentum microscopy is an emerging technique based on photoelectron spectroscopy for characterizing ultrafast electron dynamics and the out-of-equilibrium electronic structure of materials in the entire Brillouin zone with high efficiency. In this article, we introduce a setup for time-resolved momentum microscopy based on an energy-filtered momentum microscope coupled to a custom-made high-harmonic generation photon source driven by a multi-100 kHz commercial Yb-ultrafast laser that delivers fs pulses in the extreme ultraviolet range. The laser setup included a nonlinear pulse compression stage employing spectral broadening in a Herriott-type bulk-based multi-pass cell. This element allows flexible tuning of the driving pulse duration, providing a versatile time-resolved momentum microscopy setup featuring two operational modes designed to enhance either the energy or time resolution. We show the capabilities of the system by tracing ultrafast electron dynamics in the conduction band valleys of a bulk crystal of the 2D semiconductor WS2. Using uncompressed driving laser pulses, we demonstrated an energy resolution better than (107 ± 2) meV, while compressed pulses lead to a time resolution better than (48.8 ± 17) fs.
Ultrasensitive detection of remote acoustic vibrations at 300  m distance by optical feedback enhancement
Authors: Tian Mingwang , Xu Xin , Chen Sihong , Feng Zhipeng , Tan Yidong
Published: July 2024

Sensitive detection of remote vibrations at nanometer scale owns promising potential applications such as geological exploration, architecture, and public security. Nevertheless, how to detect remote vibration information with high sensitivity and anti-disturbance has become a major challenge. Reported current non-contact measurement methods are difficult to simultaneously possess characteristics of high light intensity sensitivity, long working distance, high vibration response sensitivity, and anti-disturbance of ambient light. Here, we propose a polarization-modulated laser frequency-shifted feedback interferometry method with the above characteristics, to obtain remote vibration information. The method can directly measure non-cooperative targets without the need for any cooperative markers. In each interference cycle, the energy as low as 2.3 photons can be effectively responded to, and the vibration amplitude sensitivity at 300 m can reach 0.72  nm/Hz1/2 at 1 kHz. This approach provides a strategy for the ultrasensitive detection of remote vibration that is immune to electromagnetic interference.
Sperm whale demographics in the Gulf of Alaska and Bering Sea/Aleutian Islands: An overlooked female habitat
Authors: Posdaljian Natalie , Solsona-Berga Alba , Hildebrand John A. , Soderstjerna Caroline , Wiggins Sean M. , Lenssen Kieran , Baumann-Pickering Simone
Published: July 2024

Sperm whales exhibit sexual dimorphism and sex-specific latitudinal segregation. Females and their young form social groups and are usually found in temperate and tropical latitudes, while males forage at higher latitudes. Historical whaling data and rare sightings of social groups in high latitude regions of the North Pacific, such as the Gulf of Alaska (GOA) and Bering Sea/Aleutian Islands (BSAI), suggest a more complex distribution than previously understood. Sperm whales are the most sighted and recorded cetacean in marine mammal surveys in these regions but capturing their demographic composition and habitat use has proven challenging. This study detects sperm whale presence using passive acoustic data from seven sites in the GOA and BSAI from 2010 to 2019. Differences in click characteristics between males and females (i.e., inter-click and inter-pulse interval) was used as a proxy for animal size/sex to derive time series of animal detections. Generalized additive models with generalized estimation equations demonstrate how spatiotemporal patterns differ between the sexes. Social groups were present at all recording sites with the largest relative proportion at two seamount sites in the GOA and an island site in the BSAI. We found that the seasonal patterns of presence varied for the sexes and between the sites. Male presence was highest in the summer and lowest in the winter, conversely, social group peak presence was in the winter for the BSAI and in the spring for the GOA region, with the lowest presence in the summer months. This study demonstrates that social groups are not restricted to lower latitudes and capture their present-day habitat use in the North Pacific. It highlights that sperm whale distribution is more complex than accounted for in management protocol and underscores the need for improved understanding of sperm whale demographic composition to better understand the impacts of increasing anthropogenic threats, particularly climate change.