The application of adjuvant treatment has significantly enhanced the survival of patients with resectable non-small cell lung cancer (NSCLC) carrying driver gene mutations. However, adjuvant-targeted therapy remains controversial for some NSCLC patients carrying rare gene mutations such as RET, as there is currently a lack of confirmed randomized controlled trials demonstrating efficacy. In this report, we describe the case of a 58-year-old man with stage IIIA NSCLC who underwent complete lobectomy with selective lymph node dissection. Postoperative next-generation sequencing revealed that the patient harbored a rare KIF13A-RET fusion. The patient elected to receive adjuvant treatment with pralsetinib monotherapy and underwent serial circulating tumor DNA (ctDNA) monitoring after surgery. During follow-up, despite experiencing dose reduction and irregular medication adherence, the patient still achieved a satisfactory disease-free survival (DFS) of 27 months. Furthermore, ctDNA predicted tumor recurrence 4 months earlier than imaging techniques. The addition of bevacizumab to the original regimen upon recurrence continued to be beneficial. Pralsetinib demonstrated promising efficacy as adjuvant therapy, while ctDNA analysis offered a valuable tool for early detection of tumor recurrence. By leveraging targeted therapies and innovative monitoring techniques, we aim to improve outcomes and quality of life for NSCLC patients in the future.

This study critically reevaluates reported Biginelli-like reactions using a Kamlet-Abboud-Taft-based solvent effect model. Surprisingly, structural misassignments were discovered in certain multicomponent reactions, leading to the identification of pseudo three-component derivatives instead of the expected MCR adducts. Attempts to replicate literature conditions failed, prompting reconsideration of the described MCRs and proposed mechanisms. Electrospray ionization (tandem) mass spectrometry, NMR, melting points, elemental analyses and single-crystal X-ray analysis exposed inaccuracies in reported MCRs and allowed for the proposition of a complete catalytic cycle. Biological investigations using both pure and \"contaminated\" derivatives revealed distinctive features in assessed bioassays. A new cellular action mechanism was unveiled for a one obtained pseudo three-component adduct, suggesting similarity with the known dihydropyrimidinone Monastrol as Eg5 inhibitors, disrupting mitosis by forming monoastral mitotic spindles. Docking studies and RMSD analyses supported this hypothesis. The findings described herein underscore the necessity for a critical reexamination and potential corrections of structural assignments in several reports. This work emphasizes the significance of rigorous characterization and critical evaluation in synthetic chemistry, urging a careful reassessment of reported synthesis and biological activities associated with these compounds.

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Paraganglioma is a less prevalent disease, and paraganglioma with only secreting interleukin-6 (IL-6) has not been previously reported. A 64-year-old male patient came to the hospital with the chief complaints of fever and palpitations. The peak body temperature was 38.7°C (101.66°F). Heart rate was 110 bpm, while blood pressure was in the normal range. Antibiotics and antiviral therapies were ineffective. The levels of blood IL-6, C-reactive protein (CRP), alkaline phosphatase (ALP), platelets (PLT), glutamyltransferase (GGT), fibrinogen, and D-dimer were all elevated. Infectious diseases, auto-immune diseases, and hematological malignancy were all excluded. Nearly 10 years ago, a large retroperitoneal mass of the patient was detected by accident. Fortunately, there have been no special symptoms for the past 10 years after regular follow-up. After admission this time, PET-CT was performed. A large confounding density mass at the upper part of the abdominal and retroperitoneal area was seen, and the possibility of paraganglioma was considered. However, biochemical assays for blood and urine catecholamine and their metabolites including adrenaline, norepinephrine, 3-methoxytyramine, methoxyepinephrine, methoxynorepinephrine, and vanillylmandelic acid were all in normal range in spite of mild elevated dopamine with no significance. The whole-exome capture and sequencing of the genomic DNA of the patient showed a heterozygous mutation in the coding site of KIF1B gene (Coding: NM_015047.3:c.4660G>C, Mutation: p.Val1554Leu; chromosomal location was chr1: 10428570). The mutation at this locus of KIF1B has not been reported previously. The patient refused the surgical treatment. Because the mass burdens several important organs including the pancreas, the risk of surgery was high. Doxazosin was then administered to the patient. After taking doxazosin, the symptoms disappeared rapidly. Body temperature returned to normal range in 3 days. Heart rate decreased to approximately 90 bpm. In the following days, the levels of IL-6, CPR, ALP, platelets, GGT fibrinogen, and D-dimer continued to decrease. After 63 days of taking doxazosin, IL-6 level was completely normal. After 190 days of medication, hemoglobin (Hb) and GGT levels also returned to the normal range. After 1 year onset, the patient again underwent a blood test. Almost all blood indexes were in the normal range including IL-6.

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Neonatal hypoxic-ischemic encephalopathy is a clinical phenomenon that often results from perinatal asphyxia. To mitigate secondary neurologic injury, prompt initial assessment and diagnosis is needed to identify patients eligible for therapeutic hypothermia. However, occasionally neonates present with a clinical picture of hypoxic-ischemic encephalopathy without significant risk factors for perinatal asphyxia. We hypothesized that in patients with genetic abnormalities, the clinical manifestation of those abnormalities may overlap with hypoxic-ischemic encephalopathy criteria, potentially contributing to a causal misattribution. We reviewed 210 charts of infants meeting local protocol criteria for moderate to severe hypoxic-ischemic encephalopathy in neonatal intensive care units in Calgary, Alberta. All patients that met criteria for therapeutic hypothermia were eligible for the study. Data were collected surrounding pregnancy and birth histories, as well as any available genetic or metabolic testing including microarray, gene panels, whole-exome sequencing, and newborn metabolic screens. Twenty-eight patients had genetic testing such as microarray, whole-exome sequencing, or a gene panel, because of clinical suspicion. Ten of 28 patients had genetic mutations, including CDKL5, pyruvate dehydrogenase, CFTR, CYP21A2, ISY1, KIF1A, KCNQ2, SCN9A, MTFMT, and NPHP1. All patients lacked significant risk factors to support a moderate to severe hypoxic-ischemic encephalopathy diagnosis. Treatment was changed in 2 patients because of confirmed genetic etiology. This study demonstrates the importance of identifying genetic comorbidities as potential contributors to a hypoxic-ischemic encephalopathy phenotype in neonates. Early identification of clinical factors that support an alternate diagnosis should be considered when the patient\'s clinical picture is not typical of hypoxic-ischemic encephalopathy and could aid in both treatment decisions and outcome prognostication.

This paper presents the first report of amyotrophic lateral sclerosis (ALS) kindred due to the KIF5A p.Arg1007Lys, a splice-altering variant.
An index case was a 54-year-old male who developed progressive gait difficulty and imbalance followed by mild parkinsonism, spasticity, neuropathy, ataxia, and cognitive impairment with predominant subcortical frontal involvement. Brain MRI showed marked bilateral parietal lobes atrophy. Electromyography demonstrated chronic diffuse neurogenic changes. Due to the positive history of similar symptoms in his father and the diagnosis of ALS in 10 other family members, extensive genetic testing was pursued.
Genetic screening for GRN, C9orf72, TARDBP, SOD1, FUS, MAPT mutations, and hereditary ataxia panel, was unremarkable. Whole-exome sequencing revealed c.3020G > A (p.Arg1007Lys) mutation in the KIF5A gene, later confirmed in two affected relatives.
Similar to previous reports on KIF5A-related ALS, our index case, had a mild disease course with prolonged survival. However, as the rate of progression and survival time differed even among the same family members, other factors were probably at play. Additionally, our index case and his father displayed features overlapping ALS, spastic paraplegia, Charcot-Marie-Tooth disease type 2, and frontotemporal dementia. Therefore, we suggest considering KIF5A mutations in the differential diagnosis, particularly in the presence of overlapping features of spasticity, neuropathy, cerebellar ataxia, and dementia.

Renal-hepatic-pancreatic dysplasia type 1 (RHPD1) is a rare sporadic and autosomal recessive disorder with unknown incidence. RHPD1 is caused by biallelic pathogenic variants in NPHP3, which encode nephrocystin, an important component of the ciliary protein complex.
In this case report, we describe a male newborn who was confirmed by ultrasound to have renal enlargement with multiple cysts, pancreatic enlargement with cysts, and increased liver echogenicity, leading to the clinical diagnosis of RHPD. In addition, a compound heterozygous pathogenic variant, namely, NPHP3 c.1761G > A (p. W587*) and the c.69delC (p. Gly24Ala24*11) variant, was detected by WES. The patient was clinically and genetically diagnosed with RHPD1. At 34 h of life, the infant died of respiratory insufficiency.
This is the first published case of RHPD1 in China. This study broadens the known range of RHPD1 due to NPHP3 pathogenic variants.

The clinical data for a patient with primary lung adenocarcinoma complicated with pulmonary hamartoma, who admitted to Zunyi Medical University Hospital in September 2020, was retrospectively analyzed. The 62-years-old male visited outpatient service because of dysphagia in March 2015, and the pulmonary nodules were found. In September 2020, the computed tomography indicated the enlarged nodule in the lower lobe of left lung with lobulation, and there was ground glass nodule in the upper lobe of left lung. After thoracoscopic wedge surgery, the primary pulmonary adenocarcinoma in the upper lobe of left lung and pulmonary hamartoma in the lower lobe of left lung were confirmed by pathology. Whole exon sequencing revealed that kinesin family member 20B (KIF20B) gene was not expressed in lung adenocarcinoma, but was expressed in pulmonary hamartoma. The clinical manifestations of lung adenocarcinoma complicated with pulmonary hamartoma was not typical, which could locate in the same side and different sides of the lung. The imaging manifestations of the 2 kinds of tumors were diverse and can not be completely distinguished. The pathological examination after surgery is the gold standard, and the possibility of malignant transformation of pulmonary hamartoma should be warned.
遵义医科大学附属医院于2020年9月收治的原发性肺腺癌合并肺错构瘤患者1例，男，62岁，以吞咽困难就诊。2015年3月发现肺结节于门诊规律随访，2020年9月胸部CT显示左肺下叶结节增大、有分叶，左肺上叶有磨玻璃结节影，行胸腔镜下楔形手术，术后病理确诊为左肺上叶原发性肺腺癌、左肺下叶肺错构瘤。全外显子组测序发现驱动蛋白20(kinesin family member 20B，KIF20B)基因在肺腺癌中无表达，在肺错构瘤中有表达。肺腺癌合并肺错构瘤的临床表现不典型，可位于同侧及对侧肺叶，两者影像学表现多样，不能完全区分，手术后的病理学检查是金标准，需警惕肺错构瘤恶变的可能。.