Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries.

First Exploration of Monopole-Driven Shell Evolution above the N=126 Shell Closure: New Millisecond Isomers in

Isomer spectroscopy of heavy neutron-rich nuclei beyond the N=126 closed shell has been performed for the first time at the Radioactive Isotope Beam Factory of the RIKEN Nishina Center. New millisecond isomers have been identified at low excitation energies, 985.3(19) keV in ^{213}Tl and 874(5) keV in ^{215}Tl. The measured half-lives of 1.34(5) ms in ^{213}Tl and 3.0(3) ms in ^{215}Tl suggest spins and parities 11/2^{-} with the single proton-hole configuration πh_{11/2} as leading component. They are populated via E1 transitions by the decay of higher-lying isomeric states with proposed spin and parity 17/2^{+}, interpreted as arising from a single πs_{1/2} proton hole coupled to the 8^{+} seniority isomer in the ^{A+1}Pb cores. The lowering of the 11/2^{-} states is ascribed to an increase of the πh_{11/2} proton effective single-particle energy as the second νg_{9/2} orbital is filled by neutrons, owing to a significant reduction of the proton-neutron monopole interaction between the πh_{11/2} and νg_{9/2} orbitals. The new ms isomers provide the first experimental observation of shell evolution in the almost unexplored N>126 nuclear region below doubly magic ^{208}Pb.

Health-related quality of life in patients with CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: results from the SPOTLIGHT and GLOW clinical trials.

BACKGROUND: First-line zolbetuximab plus chemotherapy (SPOTLIGHT, mFOLFOX6; GLOW, CAPOX) significantly improved progression-free survival (PFS) and overall survival (OS) versus placebo plus chemotherapy in patients with human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors were claudin 18 isoform 2-positive in the phase III SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies. We present patient-reported outcomes (PROs) from these studies. MATERIALS AND METHODS: Health-related quality of life (HRQoL) was measured in the full analysis sets using the European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients Core Questionnaire (QLQ-C30) and Oesophago-Gastric Module (QLQ-OG25), Global Pain, and 5-level EQ-5D (EQ-5D-5L) questionnaires. Analyses focused on key PRO domains: global health status (GHS)/QoL, physical functioning, abdominal pain and discomfort, and nausea/vomiting. Least squares mean (LSM) changes from baseline and time to first definitive deterioration (TTDD) were evaluated combined across SPOTLIGHT and GLOW and for individual studies. Time to confirmed deterioration (TTCD) was evaluated independently for SPOTLIGHT and GLOW. RESULTS: The combined analysis set included 1072 patients (zolbetuximab plus chemotherapy, 537; placebo plus chemotherapy, 535). Compliance rates were similar between treatment arms. Similar trends were observed in the zolbetuximab versus placebo arms for LSM changes from baseline in key PRO domains, with no clinically meaningful deterioration. Nausea/vomiting worsened during the first few zolbetuximab cycles but later returned to baseline levels. Overall TTCD and TTDD results were similar between arms in both studies. CONCLUSIONS: Patients in SPOTLIGHT and GLOW maintained measured HRQoL relative to baseline when treated with first-line zolbetuximab added to chemotherapy. Zolbetuximab plus chemotherapy improved PFS and OS without negatively affecting HRQoL in key PRO domains compared with placebo plus chemotherapy.

The GRB221009A gamma-ray burst as revealed by the gamma-ray spectrometer onboard the KPLO (Danuri).

The strongest gamma-ray burst (GRB) of the century, GRB20221009A, has been detected by the Korean Pathfinder Lunar Orbiter Gamma-ray Spectrometer (KGRS) instrument onboard the Korean Pathfinder Lunar Orbiter (KPLO). KGRS uses a LaBr3 detector to measure GRB counts with five energy bins in the energy range from 30 keV to 12 MeV. KGRS detected GRB221009A at a distance of 1.508 million kilometers from the Earth. The full duration of the main burst was recorded between 13:20 and 13:26 on October 9, 2022 with peak counts of over 1000 times background. The dead time of KGRS reached as high as 50%, and the intrinsic gamma-ray spectrum of LaBr3 was significantly altered.

Conceptual design of a Doppler spectrometer for 102 m/s cross-field flows in tokamak divertors.

The cross-field transport in the scrape-off-layers (SOLs) and divertors in tokamaks is of a similar size to the poloidal component of the parallel flow, thereby significantly impacting the plasma transport there. However, its direct observation has been challenging because the drift velocity (102-103 m/s) is significantly below the detection limit of conventional diagnostics. To realize cross-field ion flow measurement, a variety of systematic uncertainties in the system must be narrowed down. Here, we develop a conceptual design of the Doppler spectrometry that enables us to measure the impurity flows with 102-m/s accuracy based on an in situ wavelength-calibration technique developed in the astrophysics field, the iodine-cell method. We discuss its properties and applicability. In particular, the scaling relation between wavelength accuracy and various spectroscopic parameters is newly presented, which suggests the high importance of the wavelength resolution of the system. Based on transport simulations for the JT-60SA divertor, the feasibility of the system is assessed.

Sex differences in the global burden of multidrug- resistant tuberculosis without extensive drug resistance in the general population and people living with HIV/AIDS, 1990-2019.

OBJECTIVE: Currently, human immunodeficiency virus (HIV) and multi-drug resistant tuberculosis (MDR-TB) without extensive drug resistance (XDR) are significant challenges in terms of the global burden of disease. This study aimed to evaluate the trends of the global burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR, focusing on differences in socioeconomic status and sex for 204 countries and territories across periods from 1990 to 2019. MATERIALS AND METHODS: Data from the Global Burden of Disease (GBD) 2019 study were obtained to construct a separate index measuring the burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR. Incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated for each case and group. A population-attributable fraction approach was used to assess mortality and incidence of HIV/AIDS and MDR-TB coinfection. 95% uncertainty intervals (UIs) were presented for all measures. RESULTS: Our global estimates suggest that there were approximately 450,000 (95% UI 247,000-785,000) incident cases of MDR-TB without XDR and 109,000 (43,000-210,000) deaths caused by MDR-TB without XDR among individuals who were HIV-negative in 2019. For HIV-positive individuals, the corresponding figures were approximately 47,000 (33,000-67,000) incident cases of MDR-TB and 19,000 (8,000-36,000) deaths due to MDR-TB in the same year. In 2019, higher numbers of incident cases and deaths were observed in males compared to females among individuals who were HIV-negative. Conversely, for HIV-positive individuals, females had higher numbers of incident cases and deaths compared to males. Specifically, the estimated numbers for incident cases were 23,000 (15,000-33,000) for females and 24,000 (17,000-35,000) for males, while the estimated numbers for deaths were 9,600 (4,000-17,900) for females and 9,800 (4,100-18,500) for males. Male-to-female ratios have remained above 1.0 from 1990 to 2019 in both incident cases and number of deaths for HIV-negative individuals. However, for HIV and MDR-TB coinfection, both ratios were below 1.0 in most of the time series. CONCLUSIONS: Males had more cases and deaths due to MDR-TB without XDR than females in HIV-negative patients, while females faced a higher incidence and mortality in HIV/AIDS-MDR-TB without XDR. Interventions are needed to deal with such factors, which increase the burden of coinfection among females across the world.

Hospital water environment and antibiotic use: key factors in a nosocomial outbreak of carbapenemase-producing Serratia marcescens.

BACKGROUND: The healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). AIM: To report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). METHODS: The outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case-control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analysed. FINDINGS: The outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics was associated with acquisition of KPC-SM (P < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. CONCLUSION: Our study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant micro-organisms, underscoring the necessity of enhancing infection control practices in these areas.

Patellofemoral Instability Part II: Surgical Treatment.

Treatment of patellofemoral instability in skeletally mature patients remains an important area of clinical and research interest. Both nonsurgical and surgical interventions are used to treat the underlying causes. Surgical management is the mainstay of treatment of recurrent PFI that fails nonsurgical treatment, and it is broadly classified into bony and soft-tissue procedures. Proximal bony procedures include femoral trochleoplasty, derotational osteotomies, and coronal alignment correction of the femur. Distal bony procedures include tibial tubercle transfer and derotational (supratubercle and infratubercle) osteotomies. Soft-tissue procedures consist of medial patellofemoral ligament repair or reconstruction and lateral lengthening procedures. This article is the second part of our two-article review on PFI, which focuses on surgical treatment options, their indications, outcomes, and potential complications.

Ethical Stakes for Past, Present, and Prospective Tuberculosis Isolate Research Towards a Multicultural Data Sovereignty Model for Isolate Samples in Research.

Tuberculosis (TB) is a potentially fatal infectious disease that, in Aotearoa New Zealand (NZ), inequitably affects Asian, Pacific, Middle Eastern, Latin American, and African (MELAA), and Maori people. Medical research involving genome sequencing of TB samples enables more nuanced understanding of disease strains and their transmission. This could inform highly specific health interventions. However, the collection and management of TB isolate samples for research are currently informed by monocultural biomedical models often lacking key ethical considerations. Drawing on a qualitative kaupapa Maori-consistent study, this paper reports on preliminary discussions with groups of Maori, Pacific, and Afghan people in NZ, whose communities have been harmed by TB and TB stigma. Participants' discussions highlight key concerns and meanings that ought to inform the development of guidelines and a more robust consultative process for the governance of how TB isolate samples are collected and used both retrospectively and in future research. We argue for ethical processes to be culturally nuanced and community-generated, flexible and meaningful, and situated in relation to the physical and symbolic effects of TB. We discuss the significance of Indigenous data sovereignty, rights, and kawanatanga (governorship) in shaping a multicultural data sovereignty model.

Highest fusion performance without harmful edge energy bursts in tokamak.

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.

Risk factors for in-hospital acquisition of carbapenem-resistant Enterobacterales in patients with severe burns.

BACKGROUND: Although patients with severe burns are prone to severe infections with antibiotic-resistant bacteria and inevitably have some risk factors for carbapenem-resistant Enterobacterales (CRE) acquisition, risk factors for CRE infection or colonization in these patients have not been investigated. AIM: To identify the independent risk factors for CRE acquisition in patients with severe burns. METHODS: Patients admitted to the burn intensive care unit (BICU) for acute burn care were categorized based on culture results during BICU care into the CRE group and non-CRE group, which included the carbapenem-susceptible Enterobacterales (CSE) and control groups. Clinical and microbiological factors were compared between the CRE and non-CRE groups, and between the CRE and CSE groups to identify independent risk factors for in-hospital CRE acquisition. FINDINGS: Among the included 489 patients, 101 (20.7%) and 388 (79.3%) patients were classified in the CRE and non-CRE groups, respectively. The non-CRE group included 91 (18.6%) and 297 (60.7%) patients in the CSE and control groups, respectively. In multivariate analysis between the CRE and non-CRE groups, exposure to other CRE-acquired patients (P = 0.018), abbreviated burn severity index score ≥9 (P = 0.012), and mechanical ventilation (P < 0.001) were associated with CRE acquisition. In multivariate analysis between the CRE and CSE groups, exposure to other CRE-acquired patients was associated with CRE acquisition (P = 0.048). CONCLUSION: Considering the limitation of controlling the burn severity in hospitalized patients, enhanced infection control measures for preventing in-hospital CRE transmission among patients with severe burns should be emphasized.

Accuracy of artificial intelligence-assisted growth prediction in skeletal Class I preadolescent patients using serial lateral cephalograms for a 2-year growth interval.

OBJECTIVE: To investigate the accuracy of artificial intelligence-assisted growth prediction using a convolutional neural network (CNN) algorithm and longitudinal lateral cephalograms (Lat-cephs). MATERIALS AND METHODS: A total of 198 Japanese preadolescent children, who had skeletal Class I malocclusion and whose Lat-cephs were available at age 8 years (T0) and 10 years (T1), were allocated into the training, validation, and test phases (n = 161, n = 17, n = 20). Orthodontists and the CNN model identified 28 hard-tissue landmarks (HTL) and 19 soft-tissue landmarks (STL). The mean prediction error values were defined as 'excellent,' 'very good,' 'good,' 'acceptable,' and 'unsatisfactory' (criteria: 0.5 mm, 1.0 mm, 1.5 mm, and 2.0 mm, respectively). The degree of accurate prediction percentage (APP) was defined as 'very high,' 'high,' 'medium,' and 'low' (criteria: 90%, 70%, and 50%, respectively) according to the percentage of subjects that showed the error range within 1.5 mm. RESULTS: All HTLs showed acceptable-to-excellent mean PE values, while the STLs Pog', Gn', and Me' showed unsatisfactory values, and the rest showed good-to-acceptable values. Regarding the degree of APP, HTLs Ba, ramus posterior, Pm, Pog, B-point, Me, and mandibular first molar root apex exhibited low APPs. The STLs labrale superius, lower embrasure, lower lip, point of lower profile, B', Pog,' Gn' and Me' also exhibited low APPs. The remainder of HTLs and STLs showed medium-to-very high APPs. CONCLUSION: Despite the possibility of using the CNN model to predict growth, further studies are needed to improve the prediction accuracy in HTLs and STLs of the chin area.

Nano-compositional imaging of the lanthanum silicide system at THz wavelengths.

Terahertz scattering-type scanning near-field optical microscopy (THz-sSNOM) provides a noninvasive way to probe the low frequency conductivity of materials and to characterize material compositions at the nanoscale. However, the potential capability of atomic compositional analysis with THz nanoscopy remains largely unexplored. Here, we perform THz near-field imaging and spectroscopy on a model rare-earth alloy of lanthanum silicide (La-Si) which is known to exhibit diverse compositional and structural phases. We identify subwavelength spatial variations in conductivity that is manifested as alloy microstructures down to much less than 1 µm in size and is remarkably distinct from the surface topography of the material. Signal contrasts from the near-field scattering responses enable mapping the local silicon/lanthanum content differences. These observations demonstrate that THz-sSNOM offers a new avenue to investigate the compositional heterogeneity of material phases and their related nanoscale electrical as well as optical properties.

Emergence of the isotropic Kitaev honeycomb latticeα-RuCl3and its magnetic properties.

We present a comprehensive investigation of the crystal and magnetic structures of the van der Waals antiferromagnetα-RuCl3using single crystal x-ray and neutron diffraction. The crystal structure at room temperature is a monoclinic (C2/m). However, with decreasing temperature, a remarkable first-order structural phase transition is observed, leading to the emergence of a rhombohedral (R3-) structure characterized by three-fold rotational symmetry forming an isotropic honeycomb lattice. On further cooling, a zigzag-type antiferromagnetic order develops belowTN=6∼6.6K. The critical exponent of the magnetic order parameter was determined to beß=0.11(1), which is close to the two-dimensional Ising model. Additionally, the angular dependence of the magnetic critical field of the zigzag antiferromagnetic order for the polarized ferromagnetic phase reveals a six-fold rotational symmetry within theab-plane. These findingsreflect the symmetry associated with the Ising-like bond-dependent Kitaev spin interactions and underscore the universality of the Kitaev interaction-dominated antiferromagnetic system.

Cutaneous Serratia marcescens infection in two dogs.

We describe two canine cases of cutaneous infection caused by Serratia marcescens. A 2-year-old castrated male mixed dog (Case 1) presented with multiple ulcerations on the dorsal trunk, which were observed 4 days after shampooing. A 4-year-old male wolf shepherd mix dog (Case 2) presented with ulceration and purulent discharge on the nasal bridge. Cytological examination of both cases revealed pyogranulomatous inflammatory cells with rod-like infectious agents identified as S. marcescens in aerobic bacterial culture. Both patients were treated with oral antibiotics and topical chlorhexidine. Case 1 received enrofloxacin 10 mg/kg once daily for 1 week, followed by trimethoprim/sulfamethoxazole 15 mg/kg twice daily for 3 weeks. Case 2 received doxycycline 10 mg/kg twice daily for 4 weeks. No skin lesions were detected 2 weeks after the initial administration. The antibiotics were discontinued after a total 4 weeks of administration, and the skin lesions did not reappear.

Bismuth ferrite based acetone gas sensor: evaluation of graphene oxide loading.

We report a BiFeO3/graphene oxide (BFO/GO) perovskite, synthesized using a CTAB-functionalized glycine combustion route, as a potential material for acetone gas sensing applications. The physicochemical properties of the developed perovskite were analysed using XRD, FE-SEM, TEM, HRTEM, EDAX and XPS. The gas sensing performance was analysed for various test gases, including ethanol, acetone, propanol, ammonia, nitric acid, hydrogen sulphide and trimethylamine at a concentration of 500 ppm. Among the test gases, the developed BFO showed the best selectivity towards acetone, with a response of 61% at an operating temperature of 250 °C. All the GO-loaded BFO samples showed an improved gas sensing performance compared with pristine BFO in terms of sensitivity, the response/recovery times, the transient response curves and the stability. The 1 wt% GO-loaded BiFeO3 sensor showed the highest sensitivity of 89% towards acetone (500 ppm) at an operating temperature of 250 °C. These results show that the developed perovskites have significant potential for use in acetone gas sensing applications.

Trends in flame retardant levels in upholstered furniture and children's consumer products after regulatory action in California.

In 2013, California revised its upholstered furniture flammability standard TB 117-2013 to improve fire safety without the need for flame retardant (FR) chemicals. Subsequent legislation (SB 1019) required disclosure of FR content. In 2020 California expanded restriction on FR chemicals to include juvenile products and upholstered furniture (AB 2998). To monitor trends in FR use, and assess the effectiveness of the new regulations, we analyzed 346 samples from upholstered furniture (n = 270) and children's consumer products (n = 76), collected pre- and post-regulatory intervention for added FR chemicals (i.e., ∑FR > 1000 mg/kg). Upholstered furniture samples, collected from products before enactment of the new regulations, had a median FR concentration of 41,600 mg/kg (range: 1360-92,900 mg/kg), with 100% of the foam samples and 13.7% of the textile samples containing ∑FR > 1000 mg/kg. Firemaster formulations (FM 550 and FM 600), a mixture of triphenyl phosphate (TPHP), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (BEH-TEBP) and a mixture of isopropyl- or tert-butyl-triphenyl phosphates (ITPs or TBPPs), were the most frequently detected FR (34%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCIPP; 25%), TPHP with a mixture of polybrominated diphenyl ethers (BDE-47, 99, 100, 153 and 154; 20%) and tris(2-chloroethyl) phosphate (TCEP; 11%). Upholstered furniture components collected after enactment of the new legislation had a median FR concentration of 2600 mg/kg (range: 1160-49,800 mg/kg, outlier sample 282,200 mg/kg), with 11.9% of the foam samples and no textile samples containing ∑FR > 1000 mg/kg. Of these samples, tris(1-chloro-2-propyl) phosphate (TCIPP) was the most frequently detected FR (55%), followed by TDCIPP (30%) and Firemaster (FM 550, 15%). No PBDEs were detected in the post-regulatory intervention products. Our initial work on children's products showed 15% of the samples contained ∑FR > 1000 mg/kg. In our post- AB 2998 work, no regulated children's product components failed compliance (i.e., ∑FR > 1000 mg/kg). The data confirm successful adoption of the new regulations with most samples in compliance, demonstrating the efficacy of regulatory intervention. Given these results, environmental FR exposure is expected to decrease as older FR treated consumer products are replaced with FR free products.