Background: Mathematical models are not integrated into the policy‑making process in low‑ and middle‑income countries, including India, primarily due to limited capacity in building mathematical models, lack of trust in the model findings and the reluctance of policy‑makers to apply the model findings to formulate policies. There is a perceived need to create a critical mass of trained infectious disease experts and modelers within the public health and clinical domain. Thus, with the support of the Department of Health Research (DHR), we developed a 3‑month post‑graduate (PG) certificate course on infectious disease modelling, the first of such a course in India. The first cycle of the course was delivered during July to September 2024, which produced the first cohort of 20 infectious disease modellers in the country. Methods: This paper describes the structure, content and key components of the first course along with the experiences, strengths, challenges and way forward from the participants' perspective using a mixed methods approach. Findings: Most of the participants felt that the learning objectives were clear (n = 18, 90%), course content was well organised and delivered (n = 19, 95%) and the course structure allowed all participants to fully participate (n = 19, 95%) in the learning process. The strengths of the course were: hybrid mode of delivery, well‑designed course content, theory lectures followed by practical sessions, regular trainer-trainee communication, interactive discussion forums and the 3‑day contact workshop. The key challenges were non‑availability of recorded videos, evening timings of the sessions and difficulty of some topics. Conclusions: The challenges and recommendations will feed into the subsequent course cycles. Future courses are planned to be hosted on an online platform to facilitate participant completion of the course at their own pace. More collaboration with various stakeholders, nationally and internationally, will be sought to improve the content, delivery and robustness of the program.

AbstractNovel technologies are emerging and evolving at such a rapid pace that it is difficult for companies and society to absorb them. Large mature organizations can be displaced if they fail to learn about, develop, and adopt new technologies, yet they struggle to do so. What is the best approach? Clearly there is no single best answer. This paper examines organizational models that companies have experimented with for leveraging technological discoveries and inventions to create strategic innovations that fuel new growth opportunities. I adopt Kanter's concept of newstreams as the guiding lens, because it addresses the challenges that mature firms face in their attempts to create new platforms of growth that emerging technologies enable, while maintaining the health of the mainstream core business. This notion demands an extension of ambidexterity theory beyond the exploration/exploitation dichotomy, recognizing that creating new streams of growth that ultimately become part of the mainstream organization requires elements of exploitation to enhance reliability and predictability that the mainstream requires. Five organizational approaches for SI that have been observed in practice are described and considered in light of three elements that, together, can be thought of as comprising a technological innovation strategy: (a) type of ambidextrous approach the firm adopts, (b) type of technology (general vs. special purpose), and (c) targeted market (internal vs. external). By combining theory and observation, configurations of ambidexterity type, technology type, and target market are proposed, as well as expected outcomes for each. I offer these as a research agenda whose outcome can provide important guidance to organizational leaders who are attempting to build capabilities for technological innovation that will secure their organizations' future health.

Alloimmunization during pregnancy occurs when a mother produces antibodies against fetal antigens, leading to complications like hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT). HDFN involves destruction of fetal red blood cells, potentially causing severe anemia, hydrops fetalis, and fetal death. FNAIT affects fetal platelets and possibly endothelial cells, resulting in risk of intracranial hemorrhage and brain damage. Traditional invasive methods for fetal antigen genotyping, like amniocentesis, carried miscarriage risks. The discovery of cell-free fetal DNA (cff-DNA) in maternal plasma enabled safe, non-invasive prenatal testing (NIPT). Initially used for RhD blood group typing, NIPT now covers various blood group antigens. Advances in technology have further enhanced NIPT's accuracy. Despite challenges such as low cff-DNA fractions and complex genetic variations, NIPT has become essential in managing alloimmunized pregnancies. In NIPT it is important to prevent both false positive results and false negative results. Particularly in the coming decades, more possibilities for personalized antenatal treatment for HDFN and FNAIT cases will become apparent and accurate NIPT blood group antigen typing results are crucial for guiding clinical decisions. In this paper we describe this journey and provide practical tools for the clinic.

Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) progressing after chimeric antigen receptor T-cell therapy (CAR T) have dismal outcomes. The prespecified post-CAR T expansion cohort of the ELM-1 study investigated the efficacy and safety of odronextamab, a CD20×CD3 bispecific antibody, in patients with disease progression after CAR T. Sixty patients received IV odronextamab weekly for 4 cycles followed by maintenance until progression. The primary endpoint was objective response rate (ORR) by independent central review. The median number of prior lines of therapy was 3 (range 2-9), 71.7% were refractory to CAR T, and 48.3% relapsed within 90 days of CAR T. After a median follow-up of 16.2 months, ORR and complete response (CR) rate were 48.3% and 31.7%, respectively. Responses were similar across prior CAR T products and time to relapse on CAR T. Median duration of response was 14.8 months and median duration of CR was not reached. Median progression-free survival and overall survival were 4.8 months and 10.2 months, respectively. The most common treatment-emergent adverse event was cytokine release syndrome (48.3%; no Grade ≥3 events). No cases of immune effector cell-associated neurotoxicity syndrome were reported. Grade ≥3 infections occurred in 12 patients (20.0%), two of which were COVID-19. Odronextamab monotherapy demonstrated encouraging efficacy and generally manageable safety, supporting its potential as an off-the-shelf option for post-CAR T patients. This trial was registered at www.clinicaltrials.gov as #NCT02290951.

Despite novel prophylactic regimens, chronic graft-versus-host disease (cGVHD) remains a challenging complication after allogeneic hematopoietic cell transplantation. Chronic GVHD can affect multiple organs and reduces quality of life, and treatment can cause serious side effects. In the last ten years, the drugs ibrutinib, ruxolitinib, belumosudil and axatilimab were FDA-approved for cGVHD. Here we discuss which signaling pathways and cell types are targeted, the clinical studies that were the basis for FDA-approval, and future directions for clinical research.

This study investigates whether subclinical inflammation in asymptomatic patients with inflammatory bowel disease (IBD) leads to increased medication use. In a multicenter, retrospective analysis of patients diagnosed with incidental ulcerative colitis or Crohn's disease during colorectal cancer screening (2010-2021), medication use was compared with symptomatic patients and healthy non-IBD controls. Asymptomatic patients showed a higher use of cardiovascular, antiparasitic, musculoskeletal, respiratory, and sensory organ medications up to 5 years before diagnosis. This trend suggests that a systemic inflammatory process occurs years before clinical onset of IBD, suggesting the potential for earlier diagnosis and intervention.

ABSTRACTBackgroundDouble‐hit lymphoma shows a poor prognosis, necessitating early diagnosis to improve prognosis.Case PresentationA 68‐year‐old Japanese woman presented with pain and a click in the right temporomandibular joint. The right side of her neck was acutely swollen. A biopsy of a mass lesion and lymph node suggested diffuse large B‐cell lymphoma; chromosomal analyses revealed MYC and BCL2 rearrangements. Complete response was achieved with chemotherapy. Peripheral blood stem cell transplantation was performed, but the patient relapsed. She died due to respiratory failure.ConclusionDouble‐hit lymphoma is often accompanied by cervical lymphadenopathy. Lymph node biopsy is useful for early diagnosis.

The use of biocontrol microorganisms is one of the primary techniques used in agriculture to combat the damage caused by phytopathogens. Of these, Trichoderma sp. stand out as fungi species that are naturally present in agricultural soil and can come into contact with various compounds, such as nanostructured particles (NPs), which are starting to be used as pesticides and fertilizers. They can also enter the soil through various anthropogenic activities, such as water treatment, due to the treated water can then be used for crop irrigation. As a result, microorganisms like Trichoderma come into contact with these NPs, and it is unclear whether this will affect their growth and biocontrol ability. In order to determine whether the three adsorbent materials (magnetite (Fe3O4), Al-doped magnetite (Al-Fe3O4) and silver iron oxide (Ag2-xFe xO4-x) NPs) are toxic or have an impact on the biocontrol activity, the goal of this work was to expose them to two species of Trichoderma. Finding that, at 100 ppm, Trichoderma grows successfully on Fe3O4 and Al-Fe3O4 but not in the presence of Ag2-xFe xO4-x NPs. However, interestingly, the presence of these nanomaterials helps Trichoderma to better biocontrol two Fusarium species. In addition, Al-Fe3O4 and Ag2-xFe xO4-x NPs affected the expression of mycoparasitism-associated genes. These results indicate that the use of these materials and their delivery to the environment would have a synergistic effect with Trichoderma to counteract phytopathogens of agricultural interest. Additionally, the synthesis, microstructural characterization and fluoride adsorption equilibrium of the Ag2-xFe xO4-x NPs are presented.

Significant progress in determining the molecular origins and resistance mechanisms of mantle cell lymphoma (MCL) has improved our understanding of the disease's clinical diversity. These factors greatly impact prognosis in MCL patients. Given the dynamic alterations in MCL clones and disease evolution, it is crucial to recognize high-risk prognostic factors at diagnosis and relapse. Clinical factors include a high MCL International Prognostic Index score with a high Ki-67 proliferation index; early disease progression within 24 months of first-line treatment; >3 prior lines of therapy at relapse; and an aggressive (blastoid or pleomorphic) histology. Molecular aberrations include dysregulated cyclin D1; an aberrant SOX11-CD70 axis; upregulated Musashi-2; MYC rearrangement; metabolic reprogramming; and epigenetic changes. Other factors contributing to high-risk MCL include an immune-depleted microenvironment and clone adaptability with complex chromosomal anomalies and somatic mutations in TP53, NSD2, CCND1, CDKN2A, BIRC3, SP140, KMT2D, NFkBIE, SMARCA4, and NOTCH2. Ultra-high-risk MCL is indicated by the coexistence of multiple high-risk prognostic factors in the relapse setting and can portend very short progression-free survival. As MCL treatments advance towards cellular therapies, resistance to anti-CD19 chimeric antigen receptor T-cell therapy is also observed. These findings necessitate revisiting the prognostic impact of high-risk factors, current management strategies, new bi- and tri-specific T-cell engagers, combination therapies, novel therapeutic targets, and next-generation clinical trials for high-risk MCL patients. This article provides a comprehensive update on recognizing and managing high-risk MCL, encompassing current practices and future directions.