bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Estimation of Naproxen and Ranitidine HCl by Using UV Spectrophotometer
Authors: Haque Tasnuva , Talukder Md Mesbah Uddin , Laila Susmita , Fatema Kanij , Kabir Abdul Kalam Lutful
Published: January 2009

The development of a UV Spectrophotometric method for simultaneous estimation of Ranitidine HCl and Naproxen involves absorbance measurement of Ranitidine HCl at 313 nm in pH 7.4 phosphate buffer and 314 nm in both 0.1N HCl and in water and that of Naproxen at 229 nm in pH 7.4 phosphate buffer and 232 nm in both 0.1N HCl and in water corresponding to the respective absorption maxima. Both the drugs obey Beer- Lambert's law in the range of 5-25 Î¼g/ml for Ranitidine HCl and 0.2-1.25 Î¼g/ml for Naproxen. The method developed was validated to determine its linearity, precision, reproducibility and sensitivity. The tablet formulations were evaluated for the percent content of both the drugs at the selected wavelengths and the percent potency were 98.83 and 99.15 for Naproxen and Ranitidine HCl respectively. Key words: Naproxen, Ranitidine HCl, Ultraviolet spectroscopy, marketed products.doi:10.3329/sjps.v1i1.1781 Â  S. J. Pharm. Sci. 1(1&2): 18-24
Design and In Vitro Evaluation of Chrono Modulated Theophylline Tablets
Authors: Kumar B Vijaya , Nagaraj B , Agaiah B , Rambhau D
Published: January 2009

The objective of this research work was to prepare a chrono modulated delivery system to meet chronopharmacological needs of asthma. In this study theophylline was selected as a model drug. To meet this objective we considered an initial lag phase of release for 3-5 hrs and later a rapid (surge) release phase. To achieve surge release a rapidly releasing core tablet of theophylline was developed by admixing theophylline with effervescent granules and super disintegrants. The lag phase in release was achieved by coating the EV core tablets with release retarding polymer EUDRAGIT RS-100 containing HPMC, further over coated with enteric polymer CAP. The results indicate that a rapidly releasing EV tablet of theophylline cab be developed which when coated with the polymers a lag phase of 2 hrs was achievable followed by a surge release. Key Words: Theophylline, Chrono Modulated Drug Delivery, Asthma. doi:10.3329/sjps.v1i1.1782 S. J. Pharm. Sci. 1(1&2): 25-28
Rapid Method for Species-Specific Identification and Determination of Toxigenicity of Vibrio Cholerae from Natural Aquatic Environment
Authors: Chakraborty Bidhan , Zaman Khadiza , Rahman Md Majibur
Published: January 2009

Cholera caused by toxigenic Vibrio cholerae is a major public health problem confronting developing countries, where outbreaks occur in a regular seasonal pattern and are particularly associated with poverty and poor sanitation. It is generally accepted that seven distinct pandemics of cholera have occurred since the onset of the first pandemic in 1817. Again Vibrio cholerae is capable of surviving in aquatic environments for extended periods and is considered as autochthonous species in estuarine and brackish waters. Therefore, the present study was designed to isolate V. cholerae from natural environmental samples subsequently identified by conventional and molecular biological techniques. A total number of 10 isolates were included randomly in this study based on their initial identification. The serotypes of the isolates were determined by serological test (slide agglutination) and the number of serotypes O1, O139 and non-O1/O139 were 3, 2 and 5 respectively which were reconfirmed by PCR method. Finally, the toxigenicity of the isolates was analyzed by multiplex PCR method and five (5) isolates were found to contain the ctx gene, the major virulence factor of V. cholerae. Key Words: Vibrio cholerae, Simplex PCR, Multiplex PCR, Serotypes, Toxigenicity. Â  doi:10.3329/sjps.v1i1.1811 S. J. Pharm. Sci. 1(1&2): 69-75
Clinician Burnout and Effectiveness of Guideline-Recommended Psychotherapies
Authors: Sayer Nina A. , Kaplan Adam , Nelson David B. , Wiltsey Stirman Shannon , Rosen Craig S.
Published: April 2024

Importance

Clinician burnout has been associated with clinician outcomes, but the association with patient outcomes remains unclear.

Objective

To evaluate the association between clinician burnout and the outcomes of patients receiving of guideline-recommended trauma-focused psychotherapies for posttraumatic stress disorder (PTSD).

Design, Setting, and Participants

This cohort study was set at the US Veterans Affairs Health Care System and included licensed therapists who provided trauma-focused psychotherapies and responded to an online survey between May 2 and October 8, 2019, and their patients who initiated a trauma-focused therapy during the following year. Patient data were collected through December 31, 2020. Data were analyzed from May to September 2023.

Exposures

Therapists completing the survey reported burnout with a 5-point validated measure taken from the Physician Worklife Study. Burnout was defined as scores of 3 or more.

Main Outcomes and Measures

The primary outcome was patients’ clinically meaningful improvement in PTSD symptoms according to the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Patient dropout, therapist adherence, and session spacing was assessed through electronic health records. Multivariable random-effects logistic regression examined the association of therapist burnout and clinically meaningful improvement, adjusted for case-mix.

Results

In this study, 165 of 180 (91.7%) therapists (89 [53.9%] female) completed the burnout measure and provided trauma-focused psychotherapies to 1268 patients (961 [75.8%] male) with outcome data. Fifty-eight (35.2%) therapists endorsed burnout. One third of patients (431 [34.0%]) met criterion for clinically meaningful improvement. Clinically meaningful improvement in PTSD symptoms was experienced by 120 (28.3%) of the 424 patients seen by therapists who reported burnout and 311 (36.8%) of the 844 patients seen by therapists without burnout. Burnout was associated with lower odds of clinically meaningful improvement (adjusted odds ratio [OR],0.63; 95% CI, 0.48-0.85). The odds of clinically meaningful improvement were reduced for patients who dropped out (OR, 0.15; 95% CI, 0.11-0.20) and had greater session spacing (OR, 0.80; 95% CI, 0.70-0.92). Therapist adherence was not associated with therapy effectiveness. Adjusting for dropout or session spacing did not meaningfully alter the magnitude of the association between burnout and clinically meaningful improvement.

Conclusions and Relevance

In this prospective cohort study, therapist burnout was associated with reduced effectiveness of trauma-focused psychotherapies. Studying when and how burnout affects patient outcomes may inform workplace interventions.
iChIP‐SILAC analysis identifies epigenetic regulators of CpG methylation of the p16INK4A gene
Authors: Fujita Toshitsugu , Fujii Hodaka
Published: April 2024

Allele‐specific epigenetic events regulate the expression of specific genes such as tumor suppressor genes. Methods to biochemically identify epigenetic regulators remain limited. Here, we used insertional chromatin immunoprecipitation (iChIP) to address this issue. iChIP combined with quantitative mass spectrometry identified DNA methyltransferase 1 (DNMT1) and epigenetic regulators as proteins that potentially interact with a region of the p16INK4A gene that is CpG‐methylated in one allele in HCT116 cells. Some of the identified proteins are involved in the CpG methylation of this region, and of these, DEAD‐box helicase 24 (DDX24) contributes to CpG methylation by regulating the protein levels of DNMT1. Thus, iChIP is a useful method to identify proteins which bind to a target locus of interest.
Contribution of tumour and immune cells to PD‐L1 expression as a predictive biomarker in metastatic triple‐negative breast cancer: exploratory analysis from KEYNOTE‐119
Authors: Cortes Javier , Winer Eric P , Lipatov Oleg , Im Seock‐Ah , Gonçalves Anthony , Muñoz‐Couselo Eva , Lee Keun Seok , Schmid Peter , Tamura Kenji , Testa Laura , Witzel Isabell , Ohtani Shoichiro , Hund Stephanie , Kulangara Karina , Karantza Vassiliki , Mejia Jaime A , Ma Junshui , Jelinic Petar , Huang Lingkang , Pruitt Scott K , Emancipator Kenneth
Published: April 2024

The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD‐L1) expression, as quantified by combined positive score (CPS; PD‐L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple‐negative breast cancer (mTNBC) in the phase 3 KEYNOTE‐119 study. This exploratory analysis was conducted to determine whether the expression of PD‐L1 on tumour cells contributes to the predictive value of PD‐L1 CPS in mTNBC. PD‐L1 expression in tumour samples was assessed using PD‐L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD‐L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58–0.80) for CPS, 0.55 (95% CI = 0.46–0.64) for TPS, and 0.67 (95% CI = 0.56–0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression‐free survival, and overall survival. Data from this exploratory analysis suggest that, although PD‐L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD‐L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD‐L1 expression) may improve prediction. PD‐L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types.
Durable Perovskite Solar Cells with 24.5% Average Efficiency: The Role of Rigid Conjugated Core in Molecular Semiconductors
Authors: Ren Ming , Fang Lingyi , Zhang Yuyan , Eickemeyer Felix T. , Yuan Yi , Zakeeruddin Shaik M. , Grätzel Michael , Wang Peng
Published: April 2024

Efficient and robust n‐i‐p perovskite solar cells necessitate superior organic hole‐transport materials with both mechanical and electronic prowess. Deciphering the structure–property relationship of these materials is crucial for practical perovskite solar cell applications. Through direct arylation, two high glass transition temperature molecular semiconductors, DBC‐ETPA (202 °C) and TPE‐ETPA (180 °C) are synthesized, using dibenzo[g,p]chrysene (DBC) and 1,1,2,2‐tetraphenylethene (TPE) tetrabromides with triphenylene–ethylenedioxythiophene‐dimethoxytriphenylamine (ETPA). In comparison to spiro‐OMeTAD, both semiconductors exhibit shallower HOMO energy levels, resulting in increased hole densities (generated by air oxidation doping) and accelerated hole extraction from photoexcited perovskite. Experimental and theoretical studies highlight the more rigid DBC core, enhancing hole mobility due to reduced reorganization energy and lower energy disorder. Importantly, DBC‐ETPA possesses a higher cohesive energy density, leading to lower ion diffusion coefficients and higher Young's moduli. Leveraging these attributes, DBC‐ETPA is employed as the primary hole‐transport layer component, yielding perovskite solar cells with an average efficiency of 24.5%, surpassing spiro‐OMeTAD reference cells (24.0%). Furthermore, DBC‐ETPA‐based cells exhibit superior operational stability and 85 °C thermal storage stability.
Effects of Ultrasound for Bio‐Applications
Authors: Yuan Likai , Li Qianqian , Li Zhen
Published: April 2024

Ultrasound (US), as a non‐invasive mechanical wave, has served as a visual tool for medical diagnosis and therapy for echolocation effect, cavitation effect, thermal effect, and generation of reactive oxygen species (ROS) with the aid of sonosensitizers. This review summarizes the history, effects, and biomedical applications of US, and US‐assisted cancer therapy is highlighted. The rational combination of US with near‐infrared afterglow nanoparticles, anti‐tumor prodrugs, and stimuli‐responsive nanocarriers, demonstrates the great promise for bioimaging, cancer therapy, and drug delivery, promoting US‐related technology in biomedical diagnosis and therapeutics.
A Generalized Microwave Absorption Criterion of Two‐Port Networks for Electromagnetic Interference Shielding
Authors: Sun Qing‐yin , Qin Chu , Zhai Yu‐fei , Yu Hao , Wang Min
Published: April 2024

Herein, the Z11 argument tangent is proposed as a novel criterion for assessing energy loss (absorption) of the reciprocal two‐port networks composed of the shielding material. With a simple mathematical deduction, it can be found that the relationship between the network absorption and the Z11 argument tangent is inverted. The absorption decreases with increasing the Z11 argument tangent, and the Z11 argument is approximately equal to the power factor angle. Additionally, a series of samples are presented to verify their absorptions and the Z11 argument tangents. The numerical simulations on other works are also presented to calculate the Z11 argument tangent and validate the relationship between the Z11 argument tangent and electromagnetic absorption from another side. The experiment and simulation results agree well with that of the mathematical deduction. The findings can be applied in most passive shielding materials and provide a promising approach to guiding and developing absorption‐dominated electromagnetic shielding materials for next‐generation communication applications.
Risk model for morbidity and mortality following liver surgery based on a national Japanese database
Authors: Orimo Tatsuya , Hirakawa Shinya , Taketomi Akinobu , Tachimori Hisateru , Oshikiri Taro , Miyata Hiroaki , Kakeji Yoshihiro , Shirabe Ken
Published: April 2024

Aim

We evaluated the morbidity and mortality associated with liver surgery in Japan and developed a risk model for liver resection using information from a national database.

Methods

We retrospectively reviewed 73 861 Japanese patients who underwent hepatectomy between 2014 and 2019, using information from the National Clinical Database (NCD) registrations. The primary endpoints were 30 days and in‐hospital mortality, and the secondary endpoints were postoperative complications. Logistic regression risk models for postoperative morbidity and mortality after hepatectomy were constructed based on preoperative clinical parameters and types of liver resection, and validated using a bootstrapping method.

Results

The 30‐day and in‐hospital mortality rates were 0.9% and 1.7%, respectively. Trisectionectomy, hepatectomy for gallbladder cancer, hepatectomy for perihilar cholangiocarcinoma, and poor activities of daily living were statistically significant risk factors with high odds ratios for both postoperative morbidity and mortality. Internal validations indicated that the c‐indices for 30‐day and in‐hospital mortality were 0.824 and 0.839, respectively.

Conclusions

We developed a risk model for liver resection by using a national surgical database that can predict morbidity and mortality based on preoperative factors.
Novel germline JAK2R715T mutation causing PV‐like erythrocytosis in 3 generations. Amelioration by Ropeg‐Interferon
Authors: Song Jihyun , Lanikova Lucie , Kim Soo Jin , Papadopoulos Nicolas , Meznarich Jessica , Constantinescu Stefan N. , Parsegov Brynn , Prchal Jaroslav F. , Prchal Josef T.
Published: April 2024

Polycythemia vera (PV) is a clonal disorder arising from the acquired somatic mutations of the JAK2 gene, including JAK2V617F or several others in exon 12. A 38‐year‐old female had a stroke at age 32 and found to have elevated hemoglobin, normal leukocytes, normal platelets, and tested negative for JAK2V617F and exon 12 mutations. Next generation sequencing revealed a novel mutation: JAK2R715T in the pseudokinase domain (JH2) at 47.5%. Its presence in her nail DNA confirmed a germline origin. Her mother and her son similarly had erythrocytosis and a JAK2R715T mutation. Computer modeling indicated gain‐of‐function JAK2 activity. The propositus and her mother had polyclonal myelopoiesis, ruling out another somatic mutation‐derived clonal hematopoiesis. Some erythroid progenitors of all three generations grew without erythropoietin, a hallmark of PV. The in vitro reporter assay confirmed increased activity of the JAK2R715T kinase. Similar to PV, the JAK2R715T native cells have increased STAT5 phosphorylation, augmented transcripts of prothrombotic and inflammatory genes, and decreased KLF2 transcripts. The propositus was not controlled by hydroxyurea, and JAK2 inhibitors were not tolerated; however, Ropeginterferon‐alfa‐2b (Ropeg‐IFN‐α) induced a remission. Ropeg‐IFN‐α treatment also reduced JAK2 activity in the propositus, her mother and JAK2V617F PV subjects. We report dominantly inherited erythrocytosis secondary to a novel germline JAK2R715T gain‐of‐function mutation with many but not all comparable molecular features to JAK2V617F PV. We also document a previously unreported inhibitory mechanism of JAK2 signaling by Ropeg‐IFN‐α.
A Dicopper(II)‐Based Carbonic Anhydrase Model—Quantum‐Chemical Evaluation of the Mechanistic Pathway
Authors: Velmurugan Gunasekaran , Baur Philipp , Comba Peter
Published: April 2024

The cyanobacterium Prochloron didemni, an obligate symbiont of different species of colonial ascidians, occurring in the Pacific and Indian Oceans, produces a variety of cyclic peptides. These patellamide‐type macrocycles lead to relatively stable dicopper(II) complexes that are extremely efficient carbonic anhydrase mimics, the most active model systems known so far. Importantly, it recently was shown that copper(II) is coordinated to patellamide derivatives in Prochloron cells. An interesting question therefore is, whether the biological function of patellamide‐type macrocycles is related to the catalytic activity in CO2 hydration or its reverse. Here, we present a computational study to evaluate the energetics of the catalytic cycle in search of a possible answer to these questions and compare the computed energy barriers with the experimental kinetic data. It emerges that release of the bridging carbonate is a critical step and that the catalysis product inhibits catalysis at pH values above approx. 7. Therefore, carbonate transport rather than CO2 hydrolysis is proposed as the biological function of copper(II)‐patellamide complexes in the Prochloron‐Ascidian symbiosis.
Merging High‐Pressure Syngas Metal Catalysis and Biocatalysis in Tandem One‐Pot Processes for the Synthesis of Nonchiral and Chiral Alcohols from Alkenes in Water
Authors: Bork Hannah , Naße Kim E. , Vorholt Andreas J. , Gröger Harald
Published: April 2024

While simultaneously proceeding reactions are among the most fascinating features of biosynthesis, this concept of tandem processes also offers high potential in the chemical industry in terms of less waste production and improved process efficiency and sustainability. Although examples of one‐pot chemoenzymatic syntheses exist, the combination of completely different reaction types is rare. Herein, we demonstrate that extreme “antipodes” of the “worlds of catalysis”, such as syngas‐based high‐pressure hydroformylation and biocatalyzed reduction, can be combined within a tandem‐type one‐pot process in water. No significant deactivation was found for either the biocatalyst or the chemocatalyst. A proof‐of‐concept for the one‐pot process starting from 1‐octene was established with >99 % conversion and 80 % isolated yield of the desired alcohol isomers. All necessary components for hydroformylation and biocatalysis were added to the reactor from the beginning. This concept has been extended to the enantioselective synthesis of chiral products by conducting the hydroformylation of styrene and an enzymatic dynamic kinetic resolution in a tandem mode, leading to an excellent conversion of >99 % and an enantiomeric ratio of 91 : 9 for (S)‐2‐phenylpropanol. The overall process runs in water under mild and energy‐saving conditions, without any need for intermediate isolation.
Site‐Selective Radical Aromatic C−H Functionalization of Alloxazine and Flavin through Ground‐State Single Electron Transfer
Authors: Das Agnideep , Charpentier Oscar , Hessin Cheriehan , Schleinitz Jules , Pianca David , Le Breton Nolwenn , Choua Sylvie , Grimaud Laurence , Gourlaouen Christophe , Desage‐El Murr Marine
Published: April 2024

Flavins and their alloxazine isomers are key chemical scaffolds for bioinspired electron transfer strategies. Their properties can be fine‐tuned by functional groups, which must be introduced at an early stage of the synthesis as their aromatic ring is inert towards post‐functionalization. We show that the introduction of a remote metal‐binding redox site on alloxazine and flavin activates their aromatic ring towards direct C−H functionalization. Mechanistic studies are consistent with a synthetic sequence involving ground‐state single electron transfer (SET) with an electrophilic source followed by radical‐radical coupling. This unprecedented reactivity opens new opportunities in molecular editing of flavins by direct aromatic post‐functionalization and the utility of the method is demonstrated with the site‐selective C6 functionalization of alloxazine and flavin with a CF3 group, Br or Cl, that can be further elaborated into OH and aryl for chemical diversification.
Bioproduct advances: insight into failure factors in mycelium composite fabrication
Authors: Shakir Mohammad Aliff , Ahmad Mardiana Idayu
Published: April 2024

In the evolving field of bioproducts, materials that synergize sustainability with functionality are of paramount importance. Mycelium composites, derived from intricate networks of fungal filaments, are gaining traction as innovative bioproducts that offer a compelling blend of eco‐friendliness, renewability, and adaptability. As the quest intensifies for alternatives that can mitigate the environmental toll of conventional products, mycelium‐based solutions are emerging as beacons on the sustainable bioproducts horizon. Their transition from niche innovations to mainstream applications depends on their ability to overcome a series of fabrication challenges. This review paper investigates the critical challenges faced in the fabrication of mycelium composite. It examines rigorously some essential factors leading to fabrication failure, such as contamination, inconsistent growth, insufficient moisture, inappropriate pH, and improper substrate preparation. The review offers a comprehensive analysis of each factor influencing mycelium growth and the resulting composite properties, with an emphasis on preventative and mitigating strategies. Through an in‐depth exploration of case studies detailing unsuccessful mycelium composite fabrication, the significance of understanding these failure factors is emphasized. The paper culminates in a forward‐thinking discourse on potential strategies for refining fabrication processes, and identifies promising research areas poised to enhance both the success rate and overall efficiency of mycelium composite production.
Outcomes of the transformation of follicular lymphoma to diffuse large B‐cell lymphoma in the rituximab era: A population‐based study
Authors: Zheng Wenshuai , Liu Mingjuan , Guan Lixun , Wang Shenyu
Published: April 2024

Background

Histological transformation (HT) to diffuse large B‐cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t‐DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t‐DLBCL and primary DLBCL (p‐DLBCL) in the same timeframe.

Methods

We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p‐DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t‐DLBCL.

Results

Finally, we identified 50,332 FL and 95,933 p‐DLBCL. With a median follow‐up of 119 months, 1631 patients developed t‐DLBCL. The median time from FL diagnosis to t‐DLBCL was approximately 4 years. The post‐transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t‐DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t‐DLBCL and p‐DLBCL as a whole, comparable survival was observed between p‐DLBCL and t‐DLBCL receiving radiation or watch‐and‐wait as initial therapy prior to HT.

Conclusion

The outcome of t‐DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t‐DLBCL receiving watch‐and‐wait or radiation as initial therapy before HT.
Surufatinib combined with transarterial embolization versus surufatinib monotherapy in patients with liver metastatic neuroendocrine tumors: Study protocol for a prospective, randomized, controlled trial
Authors: Li Ruizhen , Li Xiaofen , You Xin , Su Minggang , Liu Yuzhi , Ke Nengwen , Cao Dan
Published: April 2024

Background

More than half of neuroendocrine tumor (NET) patients will experience liver metastasis, and interventional therapy represented by transarterial embolization (TAE) is the main local treatment method. Surufatinib is recommended as a standard systemic treatment for advanced NETs. The efficacy and safety of surufatinib combined with TAE in the treatment of liver metastasis are undetermined. This study was conducted to compare the clinical outcome of surufatinib combined with TAE versus surufatinib monotherapy in liver metastatic NETs.

Methods

This is a prospective, multicenter, open‐label, and randomized controlled trial. Patients diagnosed with liver metastatic NETs will be enrolled. Participants are randomly assigned in a 1:1 ratio to either the experimental group or the control group. Patients will be treated with surufatinib plus TAE in the experimental group, while patients in the control group will receive surufatinib monotherapy. The primary endpoint is progression‐free survival (PFS) assessed by a blinded independent image review committee (BIIRC). The secondary endpoints are investigator‐assessed PFS, liver‐specific objective response rate (ORR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events.

Discussion

This is the first prospective study to investigate the efficacy of surufatinib combined with TAE. We expect this trial to propose a new and effective treatment strategy for liver metastatic NETs.
Off‐label prescribing of immune checkpoint inhibitor therapy at a single pediatric cancer center
Authors: Gikandi Ajami , Chi Susan N. , Yeo Kee Kiat , O'Neill Allison F. , Shulman David S. , DuBois Steven G. , Collins Natalie B.
Published: April 2024

Background

Immune checkpoint inhibitors (ICI) have improved outcomes in a variety of adult cancers and are prescribed with increasing frequency across oncology. However, patterns of off‐label use of ICI in pediatrics remain unclear.

Methods

This is a single‐institution, retrospective cohort study evaluating off‐label ICI use in pediatric and young adult patients with cancer treated at our institution from 2014 to 2022. Response was based on clinician assessment derived from clinical records. Immune‐related adverse events (iRAEs) were classified according to CTCAE v5.0.

Results

We identified 50 unique patients treated with off‐label ICI (28 with solid tumors, 20 with central nervous system (CNS) tumors, 2 with hematologic malignancies). At time of ICI initiation, only five patients (10%) had localized disease, and all but one patient was treated in the relapsed/refractory setting. All patients were treated with the FDA‐approved weight‐based dosing recommendations. Overall, there was disease control in 21 patients (42%), with best response including one complete response (melanoma), two partial responses (high‐grade glioma, CNS nongerminomatous germ cell tumor), and 18 patients with stable disease. Forty‐four patients (88%) eventually experienced disease progression. Among 22 patients (44%) experiencing iRAEs, 10 (20%) had a grade ≥3 irAE, 12 (24%) required corticosteroids, and 14 (28%) required ICI discontinuation. irAE occurrence was associated with significantly improved progression‐free survival (HR 0.35; 95% CI: 0.18 to 0.68; p = 0.002) and overall survival (HR 0.33; 95% CI: 0.17 to 0.66; p = 0.002).

Conclusions

At our institution, ICI was most commonly prescribed in the relapsed/refractory setting to patients with metastatic disease. The treatment was generally well‐tolerated in the pediatric population. The overall response rate was low, and the majority of patients eventually experienced disease progression. A few patients, however, had durable treatment responses. Further studies are needed to identify which pediatric patients are most likely to benefit from ICI.
Impact of immune‐related adverse events on survival outcomes in extensive‐stage small cell lung cancer patients treated with immune checkpoint inhibitors
Authors: Nishimura Tadashi , Fujimoto Hajime , Fujiwara Takumi , Ito Kentaro , Fujiwara Atsushi , Yuda Hisamichi , Itani Hidetoshi , Naito Masahiro , Kodama Shuji , Furuhashi Kazuki , Yagi Akihiko , Saiki Haruko , Yasuma Taro , Okano Tomohito , Tomaru Atsushi , Tanigawa Motoaki , Yoshida Masamichi , Hataji Osamu , Ibata Hidenori , D'Alessandro‐Gabazza Corina N. , Gabazza Esteban C. , Kobayashi Tetsu
Published: April 2024

Background

Immune checkpoint inhibitors have recently become the standard of care in the first‐line treatment of extensive‐stage small cell lung cancer. Although immune‐related adverse events have been reported to influence prognosis in non‐small cell lung cancer patients, few studies have investigated the prognostic value of immune‐related adverse events in small cell lung cancer patients. In this study, we evaluated the prognosis of patients who developed immune‐related adverse events after first‐line treatment with immune checkpoint inhibitor‐based chemotherapy for extensive‐stage small cell lung cancer.

Methods

We enrolled 90 patients with extensive‐stage small cell lung cancer who received immune checkpoint inhibitor‐based chemotherapy as first‐line treatment from September 2019 to December 2022 in six hospitals in Japan. The patients were categorized into groups with and without immune‐related adverse events.

Results

There were 23 patients with and 67 without immune‐related adverse events. Seventeen patients had grade 1–2 immune‐related adverse events, and nine (including overlapping cases) had grade ≥3. The most frequent immune‐related adverse event was a skin rash. The median survival time was 22 months in patients with immune‐related adverse events and 9.3 months in patients without immune‐related adverse events. The hazard ratio was 0.40 (95% confidence interval: 0.19–0.83, p = 0.013).

Conclusions

The results of this study show that immune‐related adverse events are associated with improved survival outcomes in patients with extensive‐stage small cell lung cancer.
Respiratory distress in a neonate: Inflation of a third branchial anomaly with positive airway pressure
Authors: Li Chantal , Siu Jennifer M. , Woodward Mary‐Angela , Wolter Nikolaus E.
Published: April 2024

Key Clinical Message

Positive airway pressure from noninvasive ventilation is an essential tool for many pediatric patients with respiratory distress. We present a case of an unknown third branchial anomaly that was diagnosed following inflation with continuous positive airway pressure (CPAP), which exacerbated the infant's respiratory distress.
Acute acalculous cholecystitis complicated by infectious mononucleosis caused by cytomegalovirus
Authors: Ide Noriko , Hirata Risa , Motomura So , Tago Masaki
Published: April 2024

Key Clinical Message

When seeing patients who present with atypical lymphocytes and abdominal pain without accompanying symptoms of pharyngitis or lymphadenopathy, acalculous cholecystitis caused by CMV infection should be considered as a differential diagnosis.

A teenage man presented with a fever and epigastric pain. The patient tested positive for cytomegalovirus IgG and IgM. Abdominal ultrasonography and contrast‐enhanced CT revealed hepatosplenomegaly and gallbladder wall thickening. MRI did not identify gallstones or tumorous lesions. He was diagnosed with infectious mononucleosis and acalculous cholecystitis caused by cytomegalovirus.
Understanding the Remarkable Stability of Well‐Defined Dinuclear Copper(I) Carbene Complexes
Authors: Bienenmann Roel L. M. , de Vries Marianne R. , Lutz Martin , Broere Daniël L. J.
Published: April 2024

The synthesis of a well‐defined dicopper carbene complex supported by the PNNP (2,7‐bis(di‐tert‐butylphosphaneyl)methyl‐1,8‐naphthyridine) expanded pincer ligand is reported. This carbene complex is remarkably stable, even in the presence of air and water. The reactivity of this complex was explored towards typical carbene transfer substrates and its electronic structure was investigated. Using a combination of experiments and DFT calculations, the principles that underly the stability of dinuclear carbene complexes are probed.
Directly‐Fused Ni(II)Porphyrin Conjugated Polymers with Blocked meso‐Positions: Impact on Electrocatalytic Properties
Authors: Bansal Deepak , Ghahramanzadehasl Hadi , Cardenas‐Morcoso Drialys , Desport Jessica , Frache Gilles , Bengasi Giuseppe , Boscher Nicolas D.
Published: April 2024

The oxidative coupling reaction of two Ni(II) porphyrins meso‐substituted with three and four phenyl groups, Ni(II) 5,10,15‐(triphenyl)porphyrin (NiPh3P) and Ni(II) 5,10,15,20‐(tetraphenyl)porphyrin (NiPh4P) respectively, was investigated in a oxidative chemical vapor deposition (oCVD) process. Irrespective of the number of meso‐substituents, high‐resolution mass spectrometry evidences the formation of oligomeric species containing up to five porphyrin units. UV‐Vis‐NIR and XPS analyses of the oCVD films highlighted a strong dependence of the intermolecular coupling reaction with the substrate temperature. Specifically, higher substrate temperatures yield lowering of valence band maxima and reduction of the band gap. The formation of conjugated polymeric assemblies results in increased conductivities as compared to their sublimed counterparts. Yet, electrocatalytic measurements exhibit water oxidation onset overpotentials (308 mV for pNiPh3P and 343 mV for pNiPh4P) comparatively higher than the onset overpotential measured for the oCVD film from Ni(II) 5,15‐(diphenyl)porphyrin (pNiPh2P), i. e. 283 mV. Although DFT and comparative oCVD studies suggest the formation of directly fused porphyrins involving ‘phenyl‐mediated’ and β‐β linkages when reacting tetra‐meso‐substituted porphyrins, the present findings highlight that multiple direct fusion (β‐β/meso‐meso/β‐β or meso‐β/β‐meso) is essential for Ni(II) porphyrin‐based conjugated polymers to enable a dinuclear radical oxo‐coupling operating mechanism for water oxidation at low overpotential and durable catalytic activity.
Structural Chemistry of Titanium (IV) Oxo Clusters, Part 2: Clusters without Carboxylate or Phosphonate Ligands
Authors: Schubert Ulrich , Stöger Berthold
Published: April 2024

Homometallic titanium oxo clusters (TOC) are one of the most important groups of metal oxo clusters. In a previous article, TOC structures with carboxylato and phosphonato ligands were reviewed and categorized. This work is now extended to clusters with other ligands. Comparison of the different cluster types shows how the interplay between condensation of the titanium polyhedra by means of bridging oxygen atoms and the coordination characteristics of the ligands influences the cluster structures and allows working out basic construction principles of the cluster core.
Continuous Kolbe Electrolysis Using an Electrochemical Microreactor, Product Separation, and Electrolyte Recycling
Authors: Baumgarten Nils , Etzold Bastian J. M. , Löb Patrick , Magomajew Juri , Ziogas Athanassios
Published: April 2024

With our electrochemical microreactor and the use of an aqueous electrolyte it was possible to realize continuous Kolbe electrolysis including separation of the organic product phase, recycling of the aqueous electrolyte, and automated reconcentration of fatty acids based on inline Raman measurements. Electrolysis experiments revealed that the addition of aqueous KOH is essential to decrease the KHCO3 concentration and to stabilize the pH value of the electrolyte. Stable conversion (63–58 %) and Kolbe selectivity (90–92 %) could be achieved within 75 min. Removal of KHCO3 before reconcentration was provided as possible solution to maintain performance for increased electrolysis times.
BF3 Complexing Phosphate/Phosphonate Ionic Liquids: Synthesis, Characterization and Thermophysical Properties
Authors: Zeng Ji‐Jun , Liao Yuan‐Hao , An Yu , Zhao Bo , Tang Xiao‐Bo , Han Sheng , Zhang Wei , Lu Jian
Published: April 2024

A new group of BF3 complexing phosphate/phosphonate ionic liquids (ILs) [Emim][X(BF3)2] (X=dimethyl phosphate, diethyl phosphate, methyl phosphonate, and ethyl phosphonate) were synthesized and characterized. Key thermophysical properties of the new complex ionic liquids, including density, viscosity, conductivity, surface tension, solid‐liquid phase transition, and thermal stability were determined and compared with those of [Emim][X]. Some other important thermophysical properties such as isobaric thermal expansion coefficient, molecular volume, standard molar entropy, and lattice potential energy were obtained from measured density data, and the free volume was estimated by a linear equation presented in this article, while critical temperature, normal boiling temperature, and enthalpy of vaporization were estimated from measured surface tension and density data. Furthermore, Fragility study shows that [Emim][X(BF3)2] should be considered as fragile liquids, while [Emim][X] could be considered as extremely fragile liquids. The ionicity of [Emim][X(BF3)2] was predicted by Walden rule, and the result shows that these ILs fit well with Walden law. The key features of these complex ILs are their extremely low glass transition (−95.33~−98.46 °C) without melting, considerably low viscosities (33.876~58.117 mPa ⋅ s), and high values of free volume fraction (comparable to [Omim][BF4], [Emim][NTf2], and [Emim][TCB]).
Low‐lying Negative Ion States Probed in Potassium – Ethanol Collisions
Authors: Lozano Ana Isabel , Kumar Sarvesh , Pereira Pedro J. S. , Kerkeni Boutheïna , García Gustavo , Limão‐Vieira Paulo
Published: April 2024

Dissociative electron transfer in collisions between neutral potassium atoms and neutral ethanol molecules yields mainly OH−, followed by C2H5O−, O−, CH3− and CH2−. The dynamics of negative ions have been investigated by recording time‐of‐flight mass spectra in a wide range of collision energies from 17.5 to 350 eV in the lab frame, where the branching ratios show a relevant energy dependence for low/intermediate collision energies. The dominant fragmentation channel in the whole energy range investigated has been assigned to the hydroxyl anion in contrast to oxygen anion from dissociative electron attachment (DEA) experiments. This result shows the relevant role of the electron donor in the vicinity of the temporary negative ion formed allowing access to reactions which are not thermodynamically attained in DEA experiments. The electronic state spectroscopy of such negative ions, was obtained from potassium cation energy loss spectra in the forward scattering direction at 205 eV impact energy, showing a prevalent Feshbach resonance at 9.36±0.10 eV with
character, while a less pronounced
contribution assigned to a shape resonance has been obtained at 3.16±0.10 eV. Quantum chemical calculations for the lowest‐lying unoccupied molecular orbitals in the presence of a potassium atom have been performed to support the experimental findings.
Implications of Defect Density and Polymer Interactions for CO2 Capture on Amine‐Functionalized MIL‐101(Cr)
Authors: Yang Rachel A. , Cho Stanley , Hughes Sydney N. , Sarazen Michele L.
Published: April 2024

Rising anthropogenic carbon emissions have dire environmental consequences, necessitating remediative approaches, which includes use of solid sorbents. Here, aminopolymers (poly(ethylene imine) (PEI) and poly(propylene imine) (PPI)) are supported within solid mesoporous MIL‐101(Cr) to examine effects of support defect density on aminopolymer‐MOF interactions for CO2 uptake and stability during uptake‐regeneration cycles. Using simulated flue gas (10 % CO2 in He), MIL‐101(Cr)‐ρhigh (higher defect density) shows 33 % higher uptake capacity per gram adsorbent than MIL‐101(Cr)‐ρlow (lower defect density) at 308 K, consistent with increased availability of undercoordinated Cr adsorption sites at missing linker defects. Increasing aminopolymer weight loadings (10–50 wt.%) within MIL‐101(Cr)‐ρlow and MIL‐101(Cr)‐ρhigh increases amine efficiencies and CO2 uptake capacities relative to bare MOFs, though both incur CO2 diffusion limitations through confined, viscous polymer phases at higher (40–50 wt.%) loadings. Benchmarked against SBA‐15, lower polymer packing densities (PPI>PEI), weaker and less abundant van der Waals interactions between aminopolymers and pore walls, and open framework topology increase amine efficiencies. Interactions between amines and Cr defect sites incur amine efficiency losses but grant higher thermal and oxidative stability during uptake‐regeneration cycling. Finally, >25 % higher CO2 uptake capacities are achieved for aminopolymer/MIL‐101(Cr)‐ρhigh under humid conditions, demonstrating promise for realistic applications.
Effectiveness of population‐based recovery actions for threatened southern mountain caribou
Authors: Lamb Clayton T. , Williams Sara , Boutin Stan , Bridger Michael , Cichowski Deborah , Cornhill Kristina , DeMars Craig , Dickie Melanie , Ernst Bevan , Ford Adam , Gillingham Michael P. , Greene Laura , Heard Douglas C. , Hebblewhite Mark , Hervieux Dave , Klaczek Mike , McLellan Bruce N. , McNay R. Scott , Neufeld Lalenia , Nobert Barry , Nowak J. Joshua , Pelletier Agnès , Reid Aaron , Roberts Anne‐Marie , Russell Mike , Seip Dale , Seip Caroline , Shores Carolyn , Steenweg Robin , White Shane , Wittmer Heiko U. , Wong Mark , Zimmerman Kathryn L. , Serrouya Robert
Published: April 2024

Habitat loss is affecting many species, including the southern mountain caribou (Rangifer tarandus caribou) population in western North America. Over the last half century, this threatened caribou population's range and abundance have dramatically contracted. An integrated population model was used to analyze 51 years (1973–2023) of demographic data from 40 southern mountain caribou subpopulations to assess the effectiveness of population‐based recovery actions at increasing population growth. Reducing potential limiting factors on threatened caribou populations offered a rare opportunity to identify the causes of decline and assess methods of recovery. Southern mountain caribou abundance declined by 51% between 1991 and 2023, and 37% of subpopulations were functionally extirpated. Wolf reduction was the only recovery action that consistently increased population growth when applied in isolation, and combinations of wolf reductions with maternal penning or supplemental feeding provided rapid growth but were applied to only four subpopulations. As of 2023, recovery actions have increased the abundance of southern mountain caribou by 52%, compared to a simulation with no interventions. When predation pressure was reduced, rapid population growth was observed, even under contemporary climate change and high levels of habitat loss. Unless predation is reduced, caribou subpopulations will continue to be extirpated well before habitat conservation and restoration can become effective.
Wolbachia infection status and molecular diversity in the species of tribe Tagiadini Mabille, 1878 (Lepidoptera: Hesperiidae) collected in China
Authors: Wei Xiaoying , Zhu Jianqing , Hoffmann Ary A. , Jia Jiqin , Xiao Mengqi , Duan Feiyu , Zhang Yimin , Zhong Huimin , Ge Jingyan , Yu Weidong , Zhang Lei , Jiang Weibin
Published: April 2024

Wolbachia, one of the most ubiquitous heritable symbionts in lepidopteran insects, can cause mitochondrial introgression in related host species. We recently found mito‐nuclear discordance in the Lepidopteran tribe Tagiadini Mabille 1878 from which Wolbachia has not been reported. In this study, we found that 13 of the 46 species of Tagiadini species tested were positive for Wolbachia. Overall, 14% (15/110) of Tagiadini specimens were infected with Wolbachia and nine new STs were found from 15 isolates. A co‐phylogenetic comparison, divergence time estimation and Wolbachia recombination analysis revealed that mito‐nuclear discordance in Tagiadini species is not mediated by Wolbachia, but Wolbachia acquisition in Tagiadini appears to have occurred mainly through horizontal transmission rather than codivergence.
Phenological evolution in annual plants under light competition, changes in the growth season and mass loss
Authors: Silva Willian T. A. F. , Hansson Mats , Johansson Jacob
Published: April 2024

Flowering time is an important phenological trait in plants and a critical determinant of the success of pollination and fruit or seed development, with immense significance for agriculture as it directly affects crop yield and overall food production. Shifts in the growth season, changes in the growth season duration and changes in the production rate are environmental processes (potentially linked to climate change) that can lead to changes in flowering time in the long‐term due to selection. In contrast, biomass loss (due to, for example, herbivory or diseases) can have profound consequences for plant mass production and food security. We model the effects of these environmental processes on the flowering time evolutionarily stable strategy (ESS) of annual plants and the potential consequences for reproductive output. Our model recapitulates previous theoretical results linked to climate change and light competition and makes novel predictions about the effects of biomass loss on the evolution of flowering time. Our analysis elucidates how both the magnitude and direction of the evolutionary response can depend on whether biomass loss occurs during the earlier vegetative phase or during the later reproductive phase and on whether or not plants are adapted to grow in dense, competitive environments. Specifically, light competition generates an asymetric effect of mass loss on flowering time even when loss is indiscriminate (equal rates), with vegetative mass loss having a stronger effect on flowering time (resulting in greater ESS change) and final reproductive output.