bluuebunny/crossref_metadata_2025 huggingface dataset:
INTEGRATE IIa: A randomised, double-blind, phase III study of regorafenib versus placebo in refractory advanced gastro-oesophageal cancer (AGOC)—A study led by the Australasian Gastro-intestinal Trials Group (AGITG).
Authors: Pavlakis Nick , Shitara Kohei , Sjoquist Katrin Marie , Martin Andrew James , Jaworski Anthony , Yip Sonia , Bang Yung-Jue , Alcindor Thierry , O'Callaghan Christopher J. , Tebbutt Niall C. , Strickland Andrew , Rha Sun Young , Lee Keun-Wook , Zalcberg John Raymond , Price Timothy Jay , Simes John , Goldstein David
Published: January 2023

LBA294

Background: AGOC has limited options after second-line therapy. Regorafenib (Rego), an oral multi-targeted tyrosine kinase inhibitor (TKI) targeting angiogenic, stromal and oncogenic receptor TKs, prolonged progression free survival (PFS) versus placebo (PBO) across all regions/subgroups in the INTEGRATE phase 2 randomised trial (JCO 2016 43(23):2728-2735). INTEGRATE IIa was designed to examine if Rego improves overall survival (OS). Methods: Double-blind placebo-controlled phase 3 trial comparing Rego + best supportive care (BSC) vs PBO + BSC using 2:1 randomisation, stratified by tumour location (GO junction vs gastric), geographic region (Asia vs rest of world), prior VEGF inhibitors (Y/N). Eligibility criteria: histologically/cytologically confirmed AGOC, evaluable metastatic/locally advanced disease, failure/intolerance of ≥ 2 prior lines of therapy with a platinum agent + fluoropyrimidine. Primary objective: OS in the whole study population. OS among Asian sub-population is a key secondary objective. Target of at least 221 events from 250 patients provides 80% power to detect an OS hazard ratio (HR) of 0.67. Pooled OS analysis incorporating INTEGRATE phase 2 data is also planned. Secondary endpoints include PFS, objective response rate, safety and quality of life. Results: 251 patients enrolled (Oct16 - Sep21) from 5 countries:157 from Asia (Korea, Taiwan, Japan);169 Rego and 82 PBO. After 238 events, median OS (in months) for Rego vs PBO was 4.5 vs 4.0 (HR 0.70 [95%CI: 0.53 to 0.92]; p = 0.011) in the whole study population, with a 12 mo survival of 19% vs 6%. Median PFS was 1.8 v 1.6 (HR = 0.52; [95%CI: 0.40-0.69]; p = < .0001). After pre-planned adjustment for multiplicity, there were no statistically significant differences across regions (Asia versus non-Asia) or other pre-specified subgroups. Pooled analysis median OS was 5.0 v 4.1 (HR 0.69 [95% CI:0.56 to 0.87]; p = 0.001). Rego toxicity was similar to previously reported. Conclusions: Rego improves survival compared with PBO in advanced refractory AGOC, offering a new treatment option. This result creates a therapeutic platform for combination studies. INTEGRATE IIb is an ongoing international randomised Phase 3 trial in pre-treated patients with AGOC comparing Rego + nivolumab to standard chemotherapy (NCT0487936). Clinical trial information: NCT02773524 .
Trial in progress: Natural killer (NK) cells with TGFβ receptor I inhibitor vactosertib and IL-2 in patients with metastatic colorectal cancer or hematologic malignancies.
Authors: Selfridge J. Eva , Bajor David L , Mohamed Amr , Chakrabarti Sakti , Reese Jane , Lazarus Hillard M. , Dowlati Afshin , Mahipal Amit , Wald David
Published: January 2023

TPS273

Background: Natural killer (NK) cell therapy is emerging as a promising therapy for patients (pts) with solid tumors and hematologic malignancies with no reported toxicity associated with the cell therapy product itself. NK cell trials in solid tumors are limited by immune inhibitory tumor microenvironments that prevent trafficking and activity of donor NK cells, which is largely governed by TGFβ signaling. We recently developed a novel platform for ex vivo expansion of healthy donor NK cells. We previously showed these cells to be safe in a dose-escalation study when given without cytokine support, with early evidence of response in pts with metastatic colorectal cancer (CRC) and in pts with hematologic malignancies. IL-2 has been well-established as an important activating cytokine supporting NK cells in humans, but can also induce regulatory T cells, which further suppress NK cells by producing TGFβ. We seek to improve upon the early activity we previously observed with NK cells alone by administering concurrently with IL-2 and by limiting the inhibitory tumor microenvironment and regulatory T cells with TGFβ receptor 1 inhibitor vactosertib. Methods: This phase Ib open-label study evaluates the safety and persistence (primary objectives), and the clinical and biological activity and trafficking (secondary objectives) of our novel NK cell therapy in combination with IL-2 (aldesleukin) and TGFβ receptor 1 inhibitor vactosertib. Up to 12 pts with metastatic CRC or relapsed/refractory hematologic malignancies will be enrolled. Pts will undergo low-dose lymphodepletion with fludarabine and cyclophosphamide followed by 2 infusions of NK cells, administered 14 days apart. Concurrently, pts will receive aldesleukin subcutaneously 3 times weekly and vactosertib orally 5 consecutive days/week x4 weeks total. Pts will undergo pre- and post-treatment biopsies for quantification of NK cell trafficking and exploration of immune cell profiling changes in the tumor microenvironment. The trial is currently open to enrollment, with 1 pt accrued at time of submission. Clinical trial information: NCT05400122 .
Phase 1b study to assess the safety of neoadjuvant trifluridine/tipiracil with concurrent radiation in resectable stage II/III rectal cancer.
Authors: Chen Emerson Yu-sheng , Nabavizadeh Nima , Herzig Daniel , Korngold Elena , Kardosh Adel , Pegna Guillaume Joe , Bensch Kenneth Gregory , Anderson Eric C. , Tsikitis Vassiliki Liana , Lu Kim , Mayo Skye C. , Brinkerhoff Brian , Goodyear Shaun , Wong Melissa , Fahlman Anne , Taber Erin , Vo Johnson , Thomas Charles R. , Lopez Charles D. ,   OHSU Gastrointestinal Cancer Disease Group
Published: January 2023

TPS274

Background: Treatment of locally advanced rectal cancer currently involves tri-modal therapy with pre-operative chemo-radiation (CRT), surgery, and combination chemotherapy. Total neoadjuvant therapy (TNT) is emerging as an important treatment pathway that can increase rates of complete response (CR) leading to better overall outcomes. Novel radio-sensitizing agents may improve rates of CR. Trifluridine/tipiracil (TFD/TPI) is a novel fluoropyrimidine that has demonstrated clinical efficacy in patients with treatment-refractory metastatic colorectal cancer. Importantly, TFD/TPI has superior radio-sensitization in vitro compared to 5-fluorouracil, and we hypothesize that this can improve the tumor response of patients. This phase 1 study assesses the safety and preliminary efficacy of using TFD/TPI for long-course CRT for rectal cancer followed by FOLFOX chemotherapy in the TNT setting. Methods: NCT04104139 is a prospective, dose-finding phase I study using Bayesian Optimal Interval (BOIN) design to determine the maximum tolerated dose (MTD) of TFD/TPI with concurrent standard dose/fractionation radiation for resectable rectal cancer. Adults with previously untreated rectal adenocarcinoma, with clinical stage II (T3-4aN0) and stage III (T1-4aN1+) by MRI and endoscopy are eligible. Patients must first receive CRT with standard radiation (45-50 Gy over 25-28 fractions) followed by up to 8 cycles of standard FOLFOX, or alternatively 5 cycles of CAPOX chemotherapy. During CRT, the first dose level of TFD/TPI is PO 25mg/m2 twice a day from Mon to Fri (5 weekdays) alternating on weeks 1, 3, and 5 concurrent with 5-6 weeks of radiation. The second dose level is 30mg/m2, and third dose level is 35mg/m2. The MTD of TFD/TPI in combination with radiation is the dose corresponding to a dose limiting toxicity (DLT) probability of 30% using the BOIN design with escalation/de-escalation of each dose level occurring in cohorts of 3 participants until a maximum total of 18 participants, sub-total of 12 patients within one dose level, or another stopping rule based on serious toxicities. The primary endpoint is proportion of DLTs for TFD/TPI at MTD. Secondary endpoints include overall tolerability profile, delayed toxicities during FOLFOX, rates of clinical CR, rates of pathologic CR, and correlative biomarkers. The study was activated December 2019 and has accrued 8 of intended 18 patients. Clinical trial information: NCT04104139 .
Trial in progress: A phase 2, multicenter, open-label study of DKN-01 in combination with tislelizumab and chemotherapy as 1L therapy in patients with unresectable, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ; DisTinGuish).
Authors: Lee Keun-Wook , Moehler Markus H. , Cunningham David , Wainberg Zev A. , Uronis Hope Elizabeth , Oh Do-Youn , Kim In-Ho , Shim Byoung Yong , Sym Sun Jin , Altura Rachel A , Stilian Melissa C , Parker Elizabeth C , Klempner Samuel J
Published: January 2023

TPS484

Background: Advanced G/GEJ cancer is a major cause of cancer-related mortality requiring novel therapies. DKN-01 is a humanized mAb that binds and neutralizes DKK1. DKK1 plays a major role in WNT-pathway regulation and is overexpressed in multiple cancers. DKK1 expression is associated with poor prognosis, an immunosuppressive tumor microenvironment, and resistance to chemotherapy in G/GEJ cancer. The non-randomized Part A of DisTinGuish demonstrated durable clinical benefit in patients with G/GEJ adenocarcinoma. Higher response rates were observed in patients with high tumoral DKK1 expression, when DKN-01 was administered in combination with an anti-PD1 mAb, tislelizumab, and chemotherapy1,2. Furthermore, in Part B, durable responses were seen in 2L patients with DKK1-high G/GEJ cancers treated with a chemotherapy-free doublet regimen, DKN-01 plus tislelizumab1. Part C will evaluate the efficacy of this chemoimmunotherapy combination in a randomized fashion in treatment-naïve G/GEJ adenocarcinoma patients. Methods: Part C is an ongoing, global, randomized phase 2 open-label study evaluating DKN-01 in combination with tislelizumab + chemotherapy (CAPOX or mFOLFOX6) vs tislelizumab + chemotherapy in patients with advanced G/GEJ adenocarcinoma. Patients are randomized 1:1 and stratified by DKK1 and PD-L1 expression. Approximately 160 patients will be enrolled from 5 different countries. Key inclusion criteria include patients with HER2 negative, G/GEJ adenocarcinoma who have received no prior systemic treatment in the unresectable locally advanced/metastatic setting and can provide tumor tissue to document PD-L1 CPS and DKK1 expression, as performed at a central lab. Key exclusion criteria include prior treatment with anti-PD1/L1/L2. The primary endpoint is PFS according to RECIST v1.1 as assessed by the investigator in patients with DKK1-high tumors. Key secondary and exploratory end points include PFS, OS, ORR, DoR in patients with tumors with any level of DKK1 expression, as assessed by both investigator and by blinded, central review. Recruitment is ongoing. Clinical trial information: NCT04363801 . References SJ Klempner, et al. DKN-01 and tislelizumab ± chemotherapy as a first-line (1L) and second-line (2L) investigational therapy in advanced gastroesophageal adenocarcinoma (GEA): DisTinGuish Trial. JCO 40, no. 4_suppl, 2022, 292-292.  SJ Klempner, et al. DKN-01 and Tislelizumab + Chemotherapy as First-line (1L) Investigational Therapy in Advanced Gastroesophageal Adenocarcinoma (GEA): DisTinGuish Trial. ESMO Annual Meeting September 2022. Clinical trial information: NCT04363801 .
A phase I study of GPC3 targeted CAR-T cell therapy in advanced GPC3-expressing hepatocellular carcinoma (HCC).
Authors: Xie Changqing , Monge B. M. Cecilia , Mabry-Hrones Donna , Coffman Kelley Lauren , Hicks Stephanie , Redd Bernadette , Wood Brad , Highfill Steven , Ho Mitchell , Greten Tim F.
Published: January 2023

TPS624

Background: The mortality of hepatocellular carcinoma (HCC) is increasing worldwide, but outcome of systemic treatments in advanced HCC is suboptimal. Adoptive T-cell transfer therapy represents a promising field that exploits the ability of T-cells to recognize and eliminate their target. Targeting the tumor-associated antigen glypican- 3 (GPC3) through chimeric antigen receptors (CAR) engineered T cells is a mechanistically rational novel treatment for advanced HCC. This study aims to determine the dose and early signals of GPC3 targeted (CAR)-T cells in advanced GPC3 expressing HCC (NCT05003895). Methods: This phase I first in human dose escalation trial will study the safety and feasibility of CAR (hYP7)- T cells in advanced HCC patients expressing GPC3. Eligibility criteria includes advanced HCC, not candidates for curative interventions, progressed on first line systemic treatment, tumor GPC3 positivity of ³ 25% by IHC, Child-Pugh Class A, ³1 measurable lesion, ECOG 0 or 1, adequate organ and marrow function. ParticipantsÕ T cells collected through leukapheresis will be transduced with a lentivirus encoding the CAR construct to generate CAR expressing T cells. Patients receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine prior to the infusion of the GPC3 directed CAR-T cells (Table). The trial has a 4-level modified Fibonacci dose escalation with a minimum of 3 patients at each level and a 28-day interval between the first three patients. Response will be assessed by imaging every two months during the first year. Patients undergo close monitoring with safety assessments during the first year and are followed for life. The primary objective is to determine the MTD, DLT, safety and feasibility of anti-GPC3 CAR expressing T- cells in patients with GPC3-expressing advanced HCC. Secondary objectives include best overall response and overall survival. Exploratory objectives are multiple and include studies to evaluate the persistence and peak levels of anti-GPC3 CAR-T cells after infusion. Recruitment began in December 2021 and the two patients at dose level -1 has been treated; the planned sample size is 38 patients. Table 1 Dose Level Anti-GPC3 CAR-T Cyclophosphamide (mg/m2) Fludarabine (mg/m2) Level -1 0.3x106 CAR-T per kg bw 200 30 Level 1 0.3x106 CAR-T per kg bw 300 30 Level 2 1x106 CAR-T per kg bw 300 30 Level 3 3x106 CAR-T per kg bw 300 30. Clinical trial information: NCT05003895 .
Phase II trial of second-line regorafenib in patients with unresectable hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab: REGONEXT trial.
Authors: Cheon Jaekyung , Ryoo Baek-Yeol , Kang Beodeul , Chon Hongjae , Yoo Changhoon
Published: January 2023

TPS634

Background: Atezolizumab-bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial, and is the new standard of care for first-line treatment of advanced HCC. However, the optimal sequence of therapy after failure of Ate/Bev is unknown. Regorafenib is an oral multikinase inhibitor that blocks the activity of protein kinases involved in angiogenesis, oncogenesis, metastasis, and tumour immunity. Although regorafenib showed survival benefit as subsequent treatment in patients with advanced HCC after progression on sorafenib, the efficacy and safety of regorafenib as subsequent therapy after Ate/Bev has not been investigated yet. Therefore, we designed a phase II trial investigating the efficacy and safety of regorafenib as second-line therapy in patients with advanced HCC who progressed on first-line Ate/Bev. Methods: This is a phase II, multicenter, single-arm study in patients with advanced HCC who had progression on first-line Ate/Bev. Additional key eligibility criteria include with Eastern Cooperative Oncology Group performance status 0–1, Child-Pugh score of 5 or 6, evaluable disease per RECIST v1.1, prior administration of at least 2 cycles of Ate/Bev, and adequate organ function. Key exclusion criteria include fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma, prior regorafenib treatment, clinically significant bleeding within 28 days of enrollment and untreated or symptomatic CNS or leptomeningeal metastasis. Eligible patients will receive oral regorafenib 160 mg daily for 3 weeks of every 4-week cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, time to progression, overall response rate (ORR), disease control rate and safety. ORR and PFS is assessed per RECIST v 1.1. This study is ongoing and 18 of planned 40 patients have been enrolled. This study is prospectively registered at ClinicalTrials.gov, NCT5134532.
Trial in progress: A phase 1, first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of ASP3082 in patients with previously treated advanced solid tumors and KRAS G12D mutations.
Authors: Tolcher Anthony W. , Park Wungki , Wang Judy S. , Spira Alexander I. , Janne Pasi A. , Lee Ho-Jin , Gill Stanley , LoRusso Patricia , Herzberg Benjamin , Goldman Jonathan W. , Morgensztern Daniel , Berlin Jordan , Kasi Anup , Fujii Hisaki , Pelster Meredith
Published: January 2023

TPS764

Background: Kirsten rat sarcoma (KRAS) G12D is a point mutation observed in various cancer types including pancreatic ductal cancer, colon adenocarcinoma, and lung cancers. ASP3082 is a novel small-molecule proteolysis-targeting chimeric degrader that binds to, and selectively targets, the KRAS G12D-mutated protein for degradation via recruitment of E3 ubiquitin ligase proteins. In preclinical studies, ASP3082 selectively degraded the KRAS G12D-mutated protein and showed growth inhibitory activity in KRAS G12D-mutated cancer cells but not in KRAS -wildtype cancer cells. Notable antitumor effects of ASP3082 have been demonstrated when intravenously administered weekly in mice xenografted with KRAS G12D-mutated cancer cells. Methods: This first-in-human, open-label, multicenter, phase 1 study evaluates the safety and tolerability of ASP3082 in patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer or other solid tumors. Participants with unresectable, locally advanced, or metastatic solid tumor malignancy with documented KRAS G12D mutation are eligible for enrollment. Part 1 consists of dose-escalation cohorts of 3−12 patients receiving intravenous administration of ASP3082 in a 21-day cycle. Part 2 consists of random assignment of ≤20 patients into 2 cohorts with different ASP3082 dose levels to determine the recommended phase 2 dose. Additional tumor-specific expansion cohorts may enroll ≤20 participants per tumor type. Primary endpoints will evaluate safety and tolerability as noted by dose-limiting toxicities, adverse events, serious adverse events, laboratory test results, electrocardiograms, vital signs, physical exams, and Eastern Cooperative Oncology Group performance status. Secondary endpoints will evaluate objective response rate, duration of response, disease control rate per Response Evaluation Criteria in Solid Tumors version 1.1, pharmacokinetics of single and repeated doses of ASP3082, and changes in KRAS G12D in tumor samples. Exploratory objectives will evaluate potential biomarkers that may correlate with treatment outcomes. Tumor assessment follow-up will continue for ≤45 weeks or until progressive disease. Enrollment in Cohort 1 is complete, and enrollment to Cohort 2 began in September 2022. Clinical trial information: NCT05382559 .
Migration as a Vector of Economic Losses From Disaster-Affected Areas in the United States
Authors: DeWaard Jack , Fussell Elizabeth , Curtis Katherine J. , Whitaker Stephan D. , McConnell Kathryn , Price Kobie , Soto Michael , Anampa Castro Catalina
Published: January 2023

We introduce the consideration of human migration into research on economic losses from extreme weather disasters. Taking a comparative case study approach and using data from the Federal Reserve Bank of New York/Equifax Consumer Credit Panel, we document the size of economic losses attributable to migration from 23 disaster-affected areas in the United States before, during, and after some of the most costly hurricanes, tornadoes, and wildfires on record. We then employ demographic standardization and decomposition to determine if these losses primarily reflect changes in out-migration or the economic resources that migrants take with them. Finally, we consider the implications of these losses for changing spatial inequality in the United States. While disaster-affected areas and their populations differ in their experiences of and responses to extreme weather disasters, we generally find that, relative to the year before an extreme weather disaster, economic losses via migration from disaster-affected areas increase the year of and after the disaster, these changes primarily reflect changes in out-migration (vs. the economic resources that migrants take with them), and these losses briefly disrupt the status quo by temporarily reducing spatial inequality.
Undue Burdens: State Abortion Laws in the United States, 1994–2022
Authors: Roth Louise Marie , Lee Jennifer Hyunkyung
Published: January 2023

State laws have influenced access to abortion in the 50 years since Roe v. Wade. The 2022 Dobbs decision returned questions about the legality of abortion to the states, which increased the importance of state laws for abortion access. The objective of this study is to illustrate trends in abortion-restrictive and abortion-supportive state laws using a unique longitudinal database of reproductive health laws across the United States from 1994 to 2022. This study offers a descriptive analysis of historical trends in state-level pre-viability abortion bans, abortion method bans, efforts to dissuade abortion, TRAP (targeted regulation of abortion providers) laws, other laws that restrict reproductive choice, and laws that expand abortion access and support reproductive health. Data sources include state statutes (from Nexis Uni) and secondary sources. The data reveal that pre-viability bans, including gestation-based bans and total bans, became significantly more prevalent over time. Other abortion-restrictive laws increased from 1994 to 2022, but states also passed a growing number of laws that support reproductive health. Increasing polarization into abortion-restrictive and abortion-supportive states characterized the 1994–2022 period. These trends have implications for maternal and infant health and for racial/ethnic and income disparities.
Future directions for medicinal chemistry in the field of oligonucleotide therapeutics
Authors: Hall Jonathan
Published: January 2023

In the last decade, the field of oligonucleotide therapeutics has matured, with the regulatory approval of several single-stranded and double-stranded RNA drugs. In this Perspective, I discuss enabling developments and likely future directions in the field from the perspective of oligonucleotide chemistry.
Clinical observation on the treatment of ankle fracture with buttress plate and traditional internal fixation and its effect on GQOLI-74 score and Baird-Jackson score
Authors: Lin Zhen , Gao Lian-yun , Ruan Kang-ming , Guo Deng-bing , Chen Yan-hua , Liu Qing-ping
Published: January 2023

Objective: To explore the curative effect of buttress plate and traditional internal fixation in the treatment of ankle fracture, so as to provide potential reference for the clinical treatment of this disease.

Methods: This is a clinical comparative study. The subjects of this study were one hundred patients with ankle fracture treated in Mindong Hospital Affiliated to Fujian Medical University from January 2019 to December 2021. Enrolled patients were randomly divided into the control group and the experimental group. Patients in the control group were treated with traditional internal fixation, and those in the experimental group were provided with buttress plate. Patients were compared in several aspects such as the comprehensive quality of life assessment questionnaire (GQOLI-74), Baird-Jackson score and postoperative complications.

Results: The experimental group showed improved Baird-Jackson score after treatment, significantly higher fracture healing rate than that of the control group three months after treatment. Besides, there was no significant difference in the complications between the two groups, with good prognosis after timely treatment.

Conclusion: Internal fixation with buttress plate has obvious advantages in the treatment of ankle fractures, which can effectively improve the quality of life and promote the rapid healing of fractures. It is worthy of clinical promotion and application.

doi: https://doi.org/10.12669/pjms.39.2.6876

How to cite this: Lin Z, Gao L, Ruan K, Guo D, Chen Y, Liu Q. Clinical observation on the treatment of ankle fracture with buttress plate and traditional internal fixation and its effect on GQOLI-74 score and Baird-Jackson score. Pak J Med Sci. 2023;39(2):---------.  doi: https://doi.org/10.12669/pjms.39.2.6876

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Local Multiset Dimension of Amalgamation Graphs
Authors: Alfarisi Ridho , Susilowati Liliek , Dafik Dafik , Prabhu Savari
Published: January 2023

\textbf{Background}: One of the topics of distance in graphs is the resolving set problem. Suppose the set $W=\{s_1,s_2,…,s_k\}\subset V(G)$, the vertex representations of $\in V(G)$ is $r_m(x|W)=\{d(x,s_1),d(x,s_2),…,d(x,s_k)\}$, where $d(x,s_i)$ is the length of the shortest path of the vertex $x$ and the vertex in $W$ together with their multiplicity. The set $W$ is called a local $m$-resolving set of graphs $G$ if $r_m (v|W)\neq r_m (u|W)$ for $uv\in E(G)$. The local $m$-resolving set having minimum cardinality is called the local multiset basis and its cardinality is called the local multiset dimension of $G$, denoted by $md_l(G)$. Thus, if $G$ has an infinite local multiset dimension and then we write $md_l (G)=\infty$. \\ \textbf{Methods}: This research is pure research with exploration design. There are several stages in this research, namely we choose the special graph which is operated by amalgamation and the set of vertices and edges of amalgamation of graphs; determine the set $W\subset V(G)$; determine the vertex representation of two adjacent vertices in $G$; and prove the theorem.\\ \textbf{Results}: The results of this research are an upper bound of local multiset dimension of the amalgamation of graphs namely $md_l(Amal(G,v,m))\leq m.md_l(G)$ and their exact value of local multiset dimension of some families of graphs namely $md_l(Amal(P_n,v,m))=1$, $md_l(Amal(K_n,v,m))=\infty$, $md_l(Amal(W_n,v,m))=m. md_l(W_n)$, $md_l(Amal(F_n,v,m))=m. md_l(F_n)$ for $d(v)=n$, $md_l(Amal(F_n,v,m))=m. \lfloor\frac{n}{4}\rfloor$. \\ \textbf{Conclusions}: We have found the upper bound of a local multiset dimension. There are some graphs which attain the upper bound of local multiset dimension namely wheel graphs\\
Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp
Authors: Barazorda-Ccahuana Haruna Luz , Goyzueta-Mamani Luis Daniel , Candia Puma Mayron Antonio , Simões de Freitas Camila , de Sousa Vieria Tavares Grasiele , Pagliara Lage Daniela , Ferraz Coelho Eduardo Antonio , Chávez-Fumagalli Miguel Angel
Published: January 2023

Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies.

Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics–generalized Born surface area (MM–GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme.

Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions and hydrogen bonds enhancing enzyme–ligand coupling.

Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated.
Art, Literature, Manuscripts, Architecture – An Emperor Wants to be Remembered: Emperor Maximilian and the Ambraser Helden Buch, with a Focus on Mauritius Von Craûn
Authors: Classen Albrecht
Published: January 2023

Memory and memoria are closely related to each other, but the latter constitutes the physical, mostly public manifestation of the self through art works, writing, musical compositions, buildings, and the like. After a reflection on the current research pertaining to both aspects, this article deals with the famous Ambraser Heldenbuch compiled by Hans Ried for Emperor Maximilian I (1504–1516) as a collection of major medieval German narratives. In particular, the focus rests on the most unique verse novella, Mauritius von Craûn (ca. 1220) where knighthood and courtly love seem to reach their apogee but then abruptly fail. In an odd way, even this rather deconstructive piece of literature, preserved only in this very late manuscript, obviously contributed to Maximilian’s great effort to secure his gedechtnus, the memory by posterity of his glory and accomplishments. However, there is also a great sense of the precarious nature of this goal, hence of memoria. To understand late medieval aristocratic culture, we can rely profoundly on the efforts by that social class to establish memory as a form of self-identity.
Understanding the Durability of the Paul Biya Regime in Cameroon: A Micro-Level Approach Using Afrobarometer's Round 7 National Survey
Authors: Ratsimbaharison Adrien M. , Bongang Benn L.
Published: January 2023

Paul Biya, who has been in power in Cameroon as a prime minister from 1975 to 1982 and as a president since 1982, is now the longest-ruling non-royal national leader of the world. While this durability has baffled many observers worldwide, it has not yet attracted much attention from academia. In fact, the current literature on Cameroonian politics generally focuses on the dictatorial characteristics of the Paul Biya regime, not on its durability. The purpose of this paper is to fill this gap in the literature. Adopting a micro-level (or bottom-up) approach, we try to understand why most Cameroonian people are willing to stay under the same ruler for at least two generations. Using the Afrobarometer's round 7 national surveys in Cameroon, we apply simple statistical analyses and machine learning (or predictive analytics) to determine to what extent the Cameroonian people support their president and his regime and to identify the predictors (or determinants) of such support. As a result, we find that, despite the so-called "Anglophone crisis" and Boko Haram's attacks in the North, most Cameroonians, especially the French speakers, still approve of the job performance of Biya. The main factors behind this approval have more to do with their trust in the president himself, the approval of the job performance of their parliament members, and their regional location than with the conduct of the country's political affairs or the management of the national economy.
Paget's disease of the breast: diagnosis and management
Authors: Hudson-Phillips Sarah , Cox Kofi , Patel Puja , Al Sarakbi Wail
Published: January 2023

Paget's disease of the breast typically affects postmenopausal women and is associated with an underlying malignancy. Skin changes are a common presenting symptom, as well as a lump, nipple discharge, pain and changes to the nipple shape. Imaging options include ultrasound for women under the age of 35 years or mammogram and ultrasound for women over the age of 40 years. The definitive diagnostic investigation is a tissue core biopsy. Cases are discussed by a multidisciplinary team to decide on the optimal management strategy. Management options are typically surgical and include breast-conserving surgery or mastectomy in addition to oncoplastic techniques. Sentinel lymph node biopsy is performed in all patients undergoing surgery. Adjuvant chemotherapy, radiotherapy or endocrine therapy can be used to treat concomitant invasive disease or ductal carcinoma in situ.
Green SiC Trains
Authors: Hatori Kenji , Saito Shota , Soltau Nils , Stumpf Eugen
Published: January 2023

Mitsubishi Electric presents the key benefits of SiC power modules for railway applications
Hexagonal Ferrite MFe12O19 (M=Sr, Ba, Cu, Ni, Pb) Based Photocatalysts: Photoluminescence, Photocatalysis and Applications
Authors: Wang Shifa , Yu Xinmiao , Gao Huajing , Chen Xiangyu
Published: January 2023

Hexagonal ferrite (MFe12O19, M=Sr, Ba, Cu, Ni, Pb) is a kind of semiconductor material with excellent performance and an important magnetic material, with high chemical and thermal stability, low cost, simple preparation process, excellent optical, magnetic, wave-absorbing, dielectric, photoluminescence properties and catalytic activities have been widely used in broadcast communication, information storage, aerospace, automatic control, catalytic synthesis, medicine and biology and many other fields. This paper focuses on the application of MFe12O19-based ferrite in the field of photocatalysis, and further discusses the effect of preparation method on the photocatalytic activity of MFe12O19-based photocatalysts. The application of MFe12O19-based photocatalysts in the degradation of dyes, drugs and persistent organic pollutants (POPs) was deeply revealed, and the photocatalytic mechanisms of single-phase MFe12O19, ion-doped MFe12O19 and MFe12O19-based composite photocatalysts were also explored. The relationship between photocatalytic activity and photoluminescence properties of MFe12O19-based photocatalysts have also been investigated. This review points out the direction for further research on the application of MFe12O19-based photocatalysts in the field of photocatalysis.
Optimizing the Airflow Velocity Combinations Acting on Male Parent Rows for Hybrid Rice Pollination
Authors: Xi Te , Sun Lunqing , Wang Yongwei , Li Dongfang , Shanno Fake , Yao Fuqiang , Wang Jun
Published: January 2023

Highlights

The effect of airflow velocity on pollen distribution was investigated under a large-scale planting mode.

The response surface model between pollen distribution and airflow velocity was constructed.

Multi-objective optimization of airflow velocity combinations was carried out using a genetic algorithm.

The optimal airflow velocity ranges of the male parents are from 22.4 to 24 m/s, 23.1 to 27 m/s, and 23.5 to 24.1 m/s.

Abstract. Pollination is the key link in hybrid rice seed production. The pneumatic pollination method can significantly improve pollination efficiency under large-scale planting mode. To investigate the effect of airflow velocity on pollen distribution in hybrid rice pollination, the velocities of airflow acting on different male parent rows were taken as the experimental factors. The pollen amount in per view and the variation rate of pollen distribution in female parent rows were used as experimental indices. Field experiments were carried out using a self-made pneumatic pollination experimental platform. The results showed that when the airflow acted on the male parents in the first and second rows of the adjacent female parent, the pollen dissemination distance was short when the airflow velocity was low, and the pollen was mainly deposited in the area near the male parents. With the increase in airflow velocity, the peak pollen amount in per view in the female parent rows gradually moved away from the male parent rows. But they are all in the female parent rows of the effective area. The total amount of pollen also increased. Due to the blocking effect of the outer male parent row, the pollen dissemination was restricted when the airflow alone acted on the third male parent row. The effect of airflow velocity on pollen distribution was not obvious. The experimental results of different airflow velocities acting on the parent row alone are used as the basis. The objective functions of pollen amount, distribution variation rate, and airflow velocities of each male parent row were established by response surface methodology. The multi-objective optimization of airflow velocity combinations was carried out by a genetic algorithm. The pollen distribution under different air velocity combinations was obtained. When the optimal airflow velocity ranges of the male parents in rows 1, 2, and 3 are 22.4 to 24 m/s, 23.1 to 27 m/s, and 23.5 to 24.1 m/s, respectively, pollination is uniform and sufficient. The research results can provide a basis for the development of pneumatic pollinators and the optimization of working parameters under large-scale planting mode. Keywords: Multi-objective parameter optimization, Pneumatic pollination machinery, Response surface modeling, Rice pollination.
Policy Analysis In Spain: Actors And Institutions
Authors: Laura Chaqués-Bonafont Laura , Jordana Jacint
Published: January 2023

This chapter explains the main features of policy analysis in Spain. Considering the contributions of this edited volume, it describes how policy actors generate and share technical and political information to address social, economic, and political issues across different institutional frameworks, policy areas, and time. It argues that in recent decades a gradual transformation of policy analysis in Spain from a closed model to a more pluralist and specialized model occurred. Policy analysis in Spain has increased in terms of the number of actors involved, the issues under discussion, and the type of information for the policy process produced. In contrast to previous decades, governmental actors –mainly top public servants— joint with a small community of policy experts who traditionally participated in knowledge production lose their monopolistic position in favour of other actors. The proliferation of the number and type of actors involved in policy analysis has expanded policy analysis to multiple areas of the interest of researchers and experts, and it has also altered the policymaking process, moving towards a more complex and fragmented political scenario. It also evidences an evolution towards a new culture of reporting based on empirical sources, examining facts, applying technical knowledge, and confronting views and values to inspire public policies, overcoming the production of policy analysis just from a legalist approach.
Domestic policy analysis by international actors
Authors: Costa Oriol , León Margarita
Published: January 2023

In this chapter we look at the relationship between international organisations (IGOs) and domestic policy analysis in Spain. We do this by focusing on crisis management relations of the two most recent transborder crises: The Great Recession and the Covid-19 Pandemic. In line with the objectives of this edited volume we interrogate whether IGOS act as promoters or as producers of policy analysis and the factors that might facilitate or prevent this role. We claim that IGOs have a differentiated role depending on the type of crisis, the policy domains to which they pertain and the degree of sovereignty exercised at state level. Whilst policy actions of European institutions during the Great Recession took the form of coercion, the World health Organization acted as ‘teachers of norms and policies’ during the Covid-19 crisis.
Prisoners' Families, Emotions and Space
Authors: Adams Maria
Published: January 2023

This book will examine the emotional landscape of family relationships during the imprisonment of a family member focusing on prison visits as a key site of connection but also potential tensions. The core themes will be to explore families’ experiences interrelationship in the context of the prison spaces and those situated in public spaces, such as welfare, social services and personal spaces in the home; and how both penal and public spaces have had a significant impact on intensifying specific emotions, surrounding psychological and social hardships. Drawing on testimonies from relatives of prisoners including wives, husbands and parents, all of whom have dedicated consistent support to either male or female prisoners. The author will provide an explorative account on the families’ experience in relation to the role of space and agency; and the extent to which certain spaces have enabled families to feel empowered and to create a sense of agency. Lastly, this book will explore how families cope with incarceration and the processes used by families to feel empowered and to create a sense of autonomy.
The artificial home space: place of care or place of confinement?
Authors: Adams Maria
Published: January 2023

This chapter will use testimonies from families and observations from the author to understand how prison visiting room spaces can sustain relationships for prisoners and families. This chapter will explore whether families experienced the visiting room as being a space to recreate familial roles. Furthermore, there will be broader discussions to explore how these spaces can be a way to create a fabricated home space, in which families divulge a range of emotions. These spaces were often filled with educational and play activities which set a scene that resonated with home life. While these present positive opportunities to strengthen relationships, families also experienced a range of challenging responses including anger and resentment, since these representations of home life were often static and short-lived experiences.
Regulated Spaces
Authors: Adams Maria
Published: January 2023

This chapter will provide an alternative view to the previous one and will explore the role of the prison visiting room in monitoring and regulating the experiences of families of prisoners. This chapter will document families’ testimonies on spaces dominated by forms of social control within the prison visits, including strict security checks, body searches, or being visibly watched in the prison visit area. Families share their emotions of feeling scrutinised and being judged due to having a loved one in prison. Furthermore, families made observations about the prison layout, in which many voiced concerns about the challenges of intimacy with loved ones. This chapter will also explore social control mechanisms beyond the prison, in which many families experienced similar emotions of scrutiny on the outside of the prison, that is, in interactions with welfare agencies. These agencies are intended to provide financial and emotional support. However, families felt these agencies criminalised and judged them, due to their having a loved one in prison.
Surviving the incarceration process: resilience to time
Authors: Adams Maria
Published: January 2023

This chapter will explore how families use their agency ‘voice’ to adopt mechanisms to survive the process of incarceration. This chapter will document how incarceration affects families to manage adversity and how this is overcome. More so, this chapter will explore how families use to cope during the period of imprisonment and do some families cope better than others? Following on, this chapter will delve in to understanding the importance of social support mechanisms such as family members, friends or others from the community. Also, it is important to explore the family dynamics which occurred among relatives and their informal support networks, and how informal networks accommodate support for families to negotiate the incarceration process. This chapter will examine the importance of time and space to survive the incarceration process. Families often negotiated their time by being active or distracted. More so, this chapter will open wider discussions on the concept of distraction that has been a way to assert their agency and to manage their time in certain spaces, in which, families time often revolved around the sentence of their loved ones.
Schools and safeguarding: aligning expectations with reality
Authors: Baginsky Mary , Driscoll Jenny , Purcell Carl , Manthorpe Jill , Hickman Ben
Published: January 2023

The final chapter reinforces the key role which schools play in child protection and safeguarding and reviews the research reported in the book in the context of the austerity measures in place at the time it was conducted. The most important factors influencing the effectiveness of the multi-agency arrangements at local government level in supporting schools in the identification, referral and management of child protection and safeguarding concerns are considered, together with the implications of the increasingly fragmented educational estate for local authority oversight and support of schools’ fulfilment of their safeguarding responsibilities. The chapter summarises the evidence as to how staff in schools made decisions in relation to child protection concerns, the support they received to do so and the key contemporary challenges identified by school staff. In conclusion, it reflects on the recent Safeguarding Partnership reforms and the imperative that schools are fully engaged in multi-agency safeguarding arrangements.
Introduction
Authors: O’Leary Chris
Published: January 2023

To understand the birth of PSMT, it is important to understand the context within which it developed, as a reaction to two major and related developments in public administration in the second half of the 20th century: the Public Choice revolution, and New Public Management. Both of these raised significant questions about the motives of public servants, and proposed public sector reforms intended to improve government responsiveness, effectiveness and efficiency. This chapter explores three key Public Choice texts around the motives of public employees, those by Anthony Downs, William Niskanen and Patrick Dunleavy. It focuses on how these three authors understand and explain the motivations of public employees, and how these texts are interpreted within public service motivation, namely that rationality means self-interest and selfishness. This interpretation is challenged, as it is not consistent with the core premise of Public Choice theory.
Welfare, marginality and social liminality: life in the welfare ‘space’
Authors: Whelan Joe
Published: January 2023

This chapter begins the process of explicating the empirical materials that underpin much of the rest of the book. In doing so, it shows how a reliance on welfare as a primary strand of income can lead to experiences of marginality and material disadvantage. Coupled with this, it shows how welfare recipients can find themselves in a socially liminal ‘space’ that seems at once to be outside and in-between. Moreover, this chapter illustrates how life in this ‘space’ can consist of experiences of poverty and material disadvantage, a loss of autonomy and control, and a sense of not being able to take part in society along with feelings of social demotion.
Introduction
Authors: Pycroft Aaron , Bartollas Clemens
Published: January 2023

This chapter introduces the key themes of the book and articulates the approach taken to redemption, positioning the authors within the tradition of peacemaking criminology. A contrast between redemptive and non-redemptive criminology is outlined
Gifting Repentance
Authors: Pycroft Aaron , Bartollas Clemens
Published: January 2023

This chapter argues that through forgiveness we provide the other with the possibility to engage and repent. This gift is based on embracing the other as other and embodying the difference.